PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 32768638-3 2020 However, WZ possesses a biphasic effect on regulating CYP3A (the major metabolizing enzyme of tacrolimus), which could induce the mRNA and protein expression after long-term treatment while transiently inhibit the activity of CYP3A. Tacrolimus 94-104 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 54-59 34058078-1 2021 Because tacrolimus is predominantly metabolized by CYP3A, the blood concentration/dose (C/D) ratio is affected by CYP3A5 polymorphism. Tacrolimus 8-18 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 51-56 32986876-0 2021 Clinical significance of personalized tacrolimus dosing by adjusting to donor CYP3A-status in liver transplant recipients. Tacrolimus 38-48 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 78-83 32986876-1 2021 AIMS: Donor"s CYP3A-status (CYP3A5 genotype and CYP3A4 expression) can provide prognostic information regarding tacrolimus-metabolizing capacity of the liver graft and initial tacrolimus dosing for therapeutic blood concentrations in liver transplants. Tacrolimus 112-122 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 14-19 32986876-1 2021 AIMS: Donor"s CYP3A-status (CYP3A5 genotype and CYP3A4 expression) can provide prognostic information regarding tacrolimus-metabolizing capacity of the liver graft and initial tacrolimus dosing for therapeutic blood concentrations in liver transplants. Tacrolimus 112-122 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 48-54 32986876-1 2021 AIMS: Donor"s CYP3A-status (CYP3A5 genotype and CYP3A4 expression) can provide prognostic information regarding tacrolimus-metabolizing capacity of the liver graft and initial tacrolimus dosing for therapeutic blood concentrations in liver transplants. Tacrolimus 176-186 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 14-19 32986876-2 2021 The present work prospectively investigated whether CYP3A-status guided tacrolimus therapy has any potential clinical benefit for recipients in the early post-operative period. Tacrolimus 72-82 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 52-57 32986876-3 2021 METHODS: The contribution of preliminary assaying of donor CYP3A-status to the optimization of initial tacrolimus therapy and to the reduction of adverse events (acute rejection, infection, nephrotoxicity) was investigated in 112 liver transplant recipients (CYPtest group) comparing to 101 control patients on tacrolimus concentration guided therapy. Tacrolimus 103-113 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 59-64 33654003-0 2021 Unraveling the Genomic Architecture of the CYP3A Locus and ADME Genes for Personalized Tacrolimus Dosing. Tacrolimus 87-97 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 43-48 33654003-7 2021 We detected several CYP3A5 and CYP3A4 rare variants which could potentially affect TAC metabolism. Tacrolimus 83-86 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 31-37 32908236-0 2021 Correction: Influence of CYP3A polymorphisms on tacrolimus pharmacokinetics in kidney transplant recipients. Tacrolimus 48-58 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 25-30 32803289-7 2021 Subpopulation carrying CYP3A4*1G, CYP3A5*1, ABCB1-3435TT, or SLCO1B3-699AA was presented with enhanced increment in tacrolimus C0/D by 38.8-102.9%. Tacrolimus 116-126 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 23-29 32803289-8 2021 CONCLUSION: Moderate effect of diltiazem on tacrolimus sparing, which might relate to the polymorphisms of CYP3A4, CYP3A5, ABCB1, and SLCO1B3, was documented. Tacrolimus 44-54 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 107-113 33649515-0 2021 Functional CYP3A variants affecting tacrolimus trough blood concentrations in Chinese renal transplant recipients. Tacrolimus 36-46 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 11-16 33649515-2 2021 We analyzed the association between 58 single nucleotide polymorphisms (SNPs) across the CYP3A gene cluster and the log-transformed tacrolimus concentration/dose ratio (log (C0/D)) in 819 renal transplant recipients (Discovery cohort). Tacrolimus 132-142 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 89-94 32843687-0 2021 Influence CYP3A polymorphisms on tacrolimus pharmacokinetics in kidney transplant recipients. Tacrolimus 33-43 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 10-15 32843687-3 2021 This study aimed to determine, in kidney transplant patients, the influence of different genotypic clusters involving these SNPs CYP3A4*1B, CYP3A4*22, and CYP3A5*3 on Tacrolimus bioavailability during the first (PTP1) and the second (PTP2) posttransplant phase (PT). Tacrolimus 167-177 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 129-135 32843687-3 2021 This study aimed to determine, in kidney transplant patients, the influence of different genotypic clusters involving these SNPs CYP3A4*1B, CYP3A4*22, and CYP3A5*3 on Tacrolimus bioavailability during the first (PTP1) and the second (PTP2) posttransplant phase (PT). Tacrolimus 167-177 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 140-146 33534527-0 2021 COMMENTARY: Unraveling the Genomic Architecture of the CYP3A Locus and ADME Genes for Personalized Tacrolimus Dosing. Tacrolimus 99-109 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 55-60 32768638-3 2020 However, WZ possesses a biphasic effect on regulating CYP3A (the major metabolizing enzyme of tacrolimus), which could induce the mRNA and protein expression after long-term treatment while transiently inhibit the activity of CYP3A. Tacrolimus 94-104 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 226-231 32690569-4 2020 Tacrolimus is metabolised by the cytochrome P (CYP) 450 3A enzyme system, and utilisation of CYP 3A inducers to accelerate its clearance may be used as a successful therapy to treat tacrolimus toxicity. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 93-99 33278239-0 2021 High Intra-Patient Variability in Tacrolimus Exposure Calculated over a Long Period Is Associated with De Novo Donor-Specific Antibody Development and/or Late Rejection in Thai Kidney Transplant Patients Receiving Concomitant CYP3A4/5 Inhibitors. Tacrolimus 34-44 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 226-234 32712713-11 2020 CONCLUSIONS: Flucloxacillin decreases tacrolimus trough levels, possibly through a CYP3A4 and/or P-gp-inducing effect. Tacrolimus 38-48 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 83-89 33312896-2 2020 In order to expand successful renal transplant care to children and adolescents at the lowest possible cost, our pediatric renal transplant clinic uses a post-transplant tacrolimus-sparing strategy via inhibition of CYP3A4. Tacrolimus 170-180 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 216-222 33350247-1 2020 The purpose of this study was to investigate the inhibitory effects of the main active components of Salviae Miltiorrhizae Radix et Rhizoma on the metabolism of tacrolimus mediated by CYP3 A4/5 enzyme, so as to predict the potential drug-drug interaction(DDI) in clinical use. Tacrolimus 161-171 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 184-193 33350247-5 2020 The results showed that dihydrotanshinone I had a strong inhibitory effect on the metabolism of tacrolimus in both HLM and rCYP3 A4/5 enzyme systems, and the inhibitory potential IC_(50) in HLM was 6.0 mumol L~(-1), while the other four active components of Salviae Miltiorrhizae Radix et Rhizoma exhibited relatively weak inhibition on CYP3 A4/5 activity with inhibition rate less than 30% at 10 mumol L~(-1). Tacrolimus 96-106 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 124-133 32848756-1 2020 Tacrolimus is metabolized by CYP3A4 and CYP3A5 enzymes. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 29-35 32848756-11 2020 Steroids induce the metabolism of tacrolimus via pregnane X receptor mediated increased CYP3A4 expression, resulting in lower tacrolimus C0/D ratio in high risk patients. Tacrolimus 34-44 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 88-94 32848756-11 2020 Steroids induce the metabolism of tacrolimus via pregnane X receptor mediated increased CYP3A4 expression, resulting in lower tacrolimus C0/D ratio in high risk patients. Tacrolimus 126-136 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 88-94 32690569-4 2020 Tacrolimus is metabolised by the cytochrome P (CYP) 450 3A enzyme system, and utilisation of CYP 3A inducers to accelerate its clearance may be used as a successful therapy to treat tacrolimus toxicity. Tacrolimus 182-192 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 93-99 32013193-2 2020 Germline mutations in cytochrome P450 isoforms 4 and 5 genes (CYP3A4/5) and the ATP-binding cassette B1 gene (ABCB1) may contribute to interindividual tacrolimus PK variability, which may impact clinical outcomes among allogeneic hematopoietic stem cell transplantation (HSCT) patients. Tacrolimus 151-161 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 62-70 31721244-0 2020 A novel random forest integrative approach based on endogenous CYP3A4 phenotype for predicting tacrolimus concentrations and dosages in Chinese renal transplant patients. Tacrolimus 95-105 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 63-69 31721244-2 2020 The present study aimed to evaluate the potential of an integrative approach to predict individual tacrolimus concentrations and dosages based on endogenous CYP3A4 phenotype, CYP3A5 genotype and clinical variables. Tacrolimus 99-109 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 157-163 31721244-4 2020 RESULTS AND DISCUSSION: The results suggested that endogenous CYP3A4 phenotype was the most important determinant of tacrolimus concentrations and dose requirements. Tacrolimus 117-127 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 62-68 31721244-7 2020 WHAT IS NEW AND CONCLUSION: In summary, endogenous CYP3A4 phenotype is a critical biomarker for the determination of tacrolimus disposition. Tacrolimus 117-127 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 51-57 31721244-8 2020 This predictive RF approach based on CYP3A4 biomarker with the combination of CYP3A5*3 genotype and other clinical variables can be used for predicting tacrolimus concentrations and dosages, which may serve as a useful tool in individualized tacrolimus dosing. Tacrolimus 152-162 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 37-43 31721244-8 2020 This predictive RF approach based on CYP3A4 biomarker with the combination of CYP3A5*3 genotype and other clinical variables can be used for predicting tacrolimus concentrations and dosages, which may serve as a useful tool in individualized tacrolimus dosing. Tacrolimus 242-252 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 37-43 31955224-7 2020 RESULTS: In this article, we found multiple SNPs on CYP3A4, CYP3A5, FKBP1A, NFATC2 genes were predicted closely related to tacrolimus serum concentration, therapeutic effect which reflected by QMG score changes or even reasonable drug dose. Tacrolimus 123-133 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 52-58 32308538-10 2020 This can be explained by the increase in TAC concentration caused by CYP3A4 inhibition due to LMV and by the decrease in TAC concentration ascribed to the decrease in VRCZ concentration by CYP2C19 induction due to LMV. Tacrolimus 41-44 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 69-75 31733802-2 2020 Although dasatinib is the first-line treatment for CML, it has inhibitory activity against CYP3A4; this might increase the blood concentration of tacrolimus (administered to KT patients for immune suppression). Tacrolimus 146-156 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 91-97 32013193-4 2020 Significant associations were detected between germline variants in CYP3A4/5 and ABCB1 and PK endpoints (e.g., median steady-state tacrolimus concentrations and time to goal tacrolimus concentration). Tacrolimus 131-141 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 68-76 32013193-4 2020 Significant associations were detected between germline variants in CYP3A4/5 and ABCB1 and PK endpoints (e.g., median steady-state tacrolimus concentrations and time to goal tacrolimus concentration). Tacrolimus 174-184 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 68-76 31152598-0 2019 Prolonged-Release Tacrolimus Is Less Susceptible to Interaction With the Strong CYP3A Inhibitor Voriconazole in Healthy Volunteers. Tacrolimus 18-28 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 80-85 32999170-3 2020 Because tacrolimus, which is a well-established immunosuppressant for kidney transplantation, and vonoprazan share the CYP3A4 system for metabolism, drug interactions are anticipated upon simultaneous administration. Tacrolimus 8-18 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 119-125 31616470-0 2019 The Impact of CYP3A4*22 on Tacrolimus Pharmacokinetics and Outcome in Clinical Practice at a Single Kidney Transplant Center. Tacrolimus 27-37 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 14-20 31588879-0 2019 Impact of CYP3A4/5 and ABCB1 polymorphisms on tacrolimus exposure and response in pediatric primary nephrotic syndrome. Tacrolimus 46-56 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 10-18 31588879-1 2019 Aim: To evaluate the impact of CYP3A4*1G, CYP3A5*3 and ABCB1-C3435T polymorphisms on tacrolimus concentrations, efficacy and tolerance in pediatric primary nephrotic syndrome. Tacrolimus 85-95 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 31-37 31588879-6 2019 Conclusion: The genotypes of CYP3A4*1G and CYP3A5*3 rather than ABCB1-C3435T potentially predicted tacrolimus exposure and clinical response in pediatric primary nephrotic syndrome. Tacrolimus 99-109 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 29-35 31401678-1 2019 PURPOSE: The purpose of this study was to investigate the potential impact of CYP3A4, CYP3A5, and CYP3A7 polymorphisms on the concentration and efficacy of tacrolimus in a cohort of pediatric patients with nephrotic range proteinuria. Tacrolimus 156-166 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 78-84 31616470-1 2019 Background: Although there is evidence that the CYP3A4*22 variant should be considered in tacrolimus dosing in renal transplantation, its impact beyond tacrolimus dose requirements remains controversial. Tacrolimus 90-100 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 48-54 31616470-12 2019 Conclusion: At our transplantation center, both CYP3A5*3 and, to a lesser extent, CYP3A4*22 affect tacrolimus pharmacokinetics early after onset of therapy with consequences for steady-state treatment in routine clinical practice. Tacrolimus 99-109 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 82-88 30295407-1 2019 INTRODUCTION: Isavuconazole, a triazole antifungal, is an inhibitor of cytochrome P450 3A4, which also metabolizes tacrolimus and sirolimus. Tacrolimus 115-125 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 71-90 30861159-4 2019 In wild-type CYP3A4 rs2242480 (TT) carriers, patients who took calcium channel blockers had lower tacrolimus stable doses than those without the concomitant medications (P < 1 x 10-4 ). Tacrolimus 98-108 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 13-19 30861159-8 2019 Our finding suggested that wild-type CYP3A4 rs2242480 (TT) carriers should be more cautious to take tacrolimus when they are coadministrated with calcium channel blockers, and CYP3A5 rs776746 (AA) carriers may need higher tacrolimus dosage when they are in combination with hypertension. Tacrolimus 100-110 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 37-43 30861159-8 2019 Our finding suggested that wild-type CYP3A4 rs2242480 (TT) carriers should be more cautious to take tacrolimus when they are coadministrated with calcium channel blockers, and CYP3A5 rs776746 (AA) carriers may need higher tacrolimus dosage when they are in combination with hypertension. Tacrolimus 222-232 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 37-43 31045868-16 2019 Population PK models including CYP3A5 and CYP3A4 genotypes will be considered to guide initial tacrolimus dosing. Tacrolimus 95-105 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 42-48 31190414-3 2019 Tac is metabolized in the liver and intestine by the cytochrome P450 3A (CYP3A) isoforms CYP3A4 and CYP3A5. Tacrolimus 0-3 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-71 31190414-3 2019 Tac is metabolized in the liver and intestine by the cytochrome P450 3A (CYP3A) isoforms CYP3A4 and CYP3A5. Tacrolimus 0-3 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 73-78 31190414-3 2019 Tac is metabolized in the liver and intestine by the cytochrome P450 3A (CYP3A) isoforms CYP3A4 and CYP3A5. Tacrolimus 0-3 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 89-95 30058048-0 2019 Drug-metabolizing enzymes CYP3A as a link between tacrolimus and vitamin D in renal transplant recipients: is it relevant in clinical practice? Tacrolimus 50-60 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 26-31 30058048-1 2019 CYP3A enzymes are involved in the metabolism of calcineurin inhibitor tacrolimus as well as vitamin D. Tacrolimus 70-80 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-5 30058048-2 2019 In this review, we summarize the clinical aspects of CYP3A-mediated metabolism of tacrolimus and vitamin D with emphasis on the influence of single-nucleotide polymorphisms on tacrolimus disposition. Tacrolimus 82-92 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-58 30058048-2 2019 In this review, we summarize the clinical aspects of CYP3A-mediated metabolism of tacrolimus and vitamin D with emphasis on the influence of single-nucleotide polymorphisms on tacrolimus disposition. Tacrolimus 176-186 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-58 31261526-5 2019 The most commonly reported genotype was CYP3A53/3, which was strongly associated with cyclosporine A (CsA) and tacrolimus (FK506). Tacrolimus 111-121 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 40-49 31261526-5 2019 The most commonly reported genotype was CYP3A53/3, which was strongly associated with cyclosporine A (CsA) and tacrolimus (FK506). Tacrolimus 123-128 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 40-49 31061321-3 2019 This retrospective observational study assessed the relationship between serum iPTH levels and the blood concentration or dosage of tacrolimus, a CYP3A substrate, after oral administration in kidney transplant patients. Tacrolimus 132-142 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 146-151 29989304-1 2019 The magnitude of interaction between the CYP3A4 substrate tacrolimus and various CYP3A4 inhibitors is highly unpredictable. Tacrolimus 58-68 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 41-47 29989304-1 2019 The magnitude of interaction between the CYP3A4 substrate tacrolimus and various CYP3A4 inhibitors is highly unpredictable. Tacrolimus 58-68 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 81-87 29989304-2 2019 We investigated whether an individual"s baseline in vivo CYP3A4 activity, assessed using the oral midazolam (MDZ) probe, could be used to predict the magnitude of drug-drug interaction between tacrolimus and the potent CYP3A4 inhibitor itraconazole. Tacrolimus 193-203 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 57-63 29989304-2 2019 We investigated whether an individual"s baseline in vivo CYP3A4 activity, assessed using the oral midazolam (MDZ) probe, could be used to predict the magnitude of drug-drug interaction between tacrolimus and the potent CYP3A4 inhibitor itraconazole. Tacrolimus 193-203 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 219-225 30489455-1 2019 BACKGROUND: CYP3A4/5 and P-glycoprotein (P-gp, ABCB1) affect tacrolimus (TAC) exposure in T cells and kidney cells. Tacrolimus 61-71 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 12-20 31244435-0 2019 Association of Genetic Variants in CYP3A4, CYP3A5, CYP2C8, and CYP2C19 with Tacrolimus Pharmacokinetics in Renal Transplant Recipients. Tacrolimus 76-86 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 35-41 29479631-2 2019 Tacrolimus is metabolised in the liver and intestine by the cytochrome P450 3A (CYP3A) isoforms CYP3A4 and CYP3A5. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 60-78 29479631-2 2019 Tacrolimus is metabolised in the liver and intestine by the cytochrome P450 3A (CYP3A) isoforms CYP3A4 and CYP3A5. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 80-85 29479631-2 2019 Tacrolimus is metabolised in the liver and intestine by the cytochrome P450 3A (CYP3A) isoforms CYP3A4 and CYP3A5. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 96-102 30489455-1 2019 BACKGROUND: CYP3A4/5 and P-glycoprotein (P-gp, ABCB1) affect tacrolimus (TAC) exposure in T cells and kidney cells. Tacrolimus 73-76 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 12-20 30166405-2 2018 In a cohort of 50 renal transplant recipients who underwent quantification of CYP3A4 activity using the oral midazolam drug probe, we confirmed that CYP3A5 genotype is the single most important determinant of tacrolimus metabolite/parent ratio [CYP3A5 expressors displayed 2.7- and 2-fold higher relative exposure to 13-desmethyltacrolimus (DMT) and 31-DMT, respectively; P < 0.001]. Tacrolimus 209-219 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 78-84 30166405-4 2018 Additional analyses in 16 healthy volunteers showed that dual pharmacological inhibition of CYP3A4 and P-glycoprotein using itraconazole resulted in increased tacrolimus metabolite/parent ratios (+65%, +112%, and 25% for 13-, 15-, and 31-DMT, respectively; P < 0.01). Tacrolimus 159-169 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 92-98 29469606-0 2018 Detection of a rare CYP3A4 variant in a transplant patient characterized by a tacrolimus poor metabolizer phenotype. Tacrolimus 78-88 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 20-26 30040022-0 2018 Tacrolimus population pharmacokinetic models according to CYP3A5/CYP3A4/POR genotypes in Chinese Han renal transplant patients. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 65-71 29547545-1 2018 While tacrolimus and everolimus have common metabolic pathways through CYP3A4/5, tacrolimus is metabolized solely by CYP3A4 in recipients with the CYP3A5*3/*3. Tacrolimus 6-16 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 71-77 29547545-1 2018 While tacrolimus and everolimus have common metabolic pathways through CYP3A4/5, tacrolimus is metabolized solely by CYP3A4 in recipients with the CYP3A5*3/*3. Tacrolimus 81-91 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 117-123 29733390-1 2018 Background: Tacrolimus, a drug for prevention of rejection after kidney transplantation, has a narrow therapeutic window and is metabolized by the cytochrome P540 3A (CYP3A) system. Tacrolimus 12-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 147-165 29733390-1 2018 Background: Tacrolimus, a drug for prevention of rejection after kidney transplantation, has a narrow therapeutic window and is metabolized by the cytochrome P540 3A (CYP3A) system. Tacrolimus 12-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 167-172 29920787-2 2018 Single nucleotide polymorphisms (SNPs) in genes important to tacrolimus bioavailability and clearance (ABCB1, CYP3A4, and CYP3A5) are associated with differences in tacrolimus pharmacokinetics. Tacrolimus 61-71 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 110-116 29920787-2 2018 Single nucleotide polymorphisms (SNPs) in genes important to tacrolimus bioavailability and clearance (ABCB1, CYP3A4, and CYP3A5) are associated with differences in tacrolimus pharmacokinetics. Tacrolimus 165-175 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 110-116 29920787-6 2018 Compared with CYP3A poor metabolizers (PM), time to therapeutic tacrolimus trough was increased by 5.1 +- 1.6 days for CYP3A extensive metabolizers (EM, P < 0.001). Tacrolimus 64-74 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 119-124 29804290-0 2018 Tacrolimus Elimination in Four Patients With a CYP3A5*3/*3 CYP3A4*22/*22 Genotype Combination. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 59-65 29804290-1 2018 Cytochrome P450 3A5 (CYP3A5) and cytochrome P450 3A4 (CYP3A4) are the predominate enzymes responsible for tacrolimus metabolism. Tacrolimus 106-116 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 33-52 29804290-1 2018 Cytochrome P450 3A5 (CYP3A5) and cytochrome P450 3A4 (CYP3A4) are the predominate enzymes responsible for tacrolimus metabolism. Tacrolimus 106-116 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 54-60 29804290-2 2018 The presence of CYP3A4 and CYP3A5 genetic variants significantly affects tacrolimus clearance and dose requirements. Tacrolimus 73-83 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 16-22 29546446-0 2018 CYP3A4 and GCK genetic polymorphisms are the risk factors of tacrolimus-induced new-onset diabetes after transplantation in renal transplant recipients. Tacrolimus 61-71 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 29546446-1 2018 PURPOSE: We intend to investigate the association between tacrolimus-induced new-onset diabetes after transplantation (NODAT) and polymorphisms of CYP3A4, CYP3A5, ATP-binding cassette transporter sub-family C member 8 (ABCC8), and glucokinase (GCK) in renal transplant recipients. Tacrolimus 58-68 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 147-153 29546446-10 2018 CONCLUSIONS: The polymorphisms of CYP3A4 *18B and GCK G-30A were related to NODAT induced by tacrolimus. Tacrolimus 93-103 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 34-40 29160300-0 2018 Genome-wide association study identifies the common variants in CYP3A4 and CYP3A5 responsible for variation in tacrolimus trough concentration in Caucasian kidney transplant recipients. Tacrolimus 111-121 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 64-70 29160300-1 2018 The immunosuppressant tacrolimus (TAC) is metabolized by both cytochrome P450 3A4 (CYP3A4) and CYP3A5 enzymes. Tacrolimus 22-32 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 62-81 29160300-1 2018 The immunosuppressant tacrolimus (TAC) is metabolized by both cytochrome P450 3A4 (CYP3A4) and CYP3A5 enzymes. Tacrolimus 22-32 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 83-89 29615122-0 2018 Effect of CYP3 A4, CYP3 A5 and ABCB1 gene polymorphisms on the clinical efficacy of tacrolimus in the treatment of nephrotic syndrome. Tacrolimus 84-94 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 10-17 29629825-0 2018 CYP3A pharmacogenetic association with tacrolimus pharmacokinetics differs based on route of drug administration. Tacrolimus 39-49 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-5 29629825-4 2018 In addition to CYP3A5, other pharmacogenes associated with CYP3A activity, including CYP3A4, CYP3A7 and POR have also been identified as predictors of tacrolimus exposure. Tacrolimus 151-161 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 15-20 29629825-4 2018 In addition to CYP3A5, other pharmacogenes associated with CYP3A activity, including CYP3A4, CYP3A7 and POR have also been identified as predictors of tacrolimus exposure. Tacrolimus 151-161 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 85-91 28945011-1 2018 Schisantherin A and schisandrin A, the most abundant active ingredients of Wuzhi capsule, are known to inhibit tacrolimus metabolism by inhibiting CYP3A4/5. Tacrolimus 111-121 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 147-153 28777242-1 2017 OBJECTIVES: Several genetic factors were identified to be responsible for interidividual variability in tacrolimus (TAC) pharmacokinetics, with the predominant role of CYP3A5 and CYP3A4 polymorphisms. Tacrolimus 104-114 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 179-185 29256966-0 2018 Influence of donor liver CYP3A4*20 loss-of-function genotype on tacrolimus pharmacokinetics in transplanted patients. Tacrolimus 64-74 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 25-31 29256966-2 2018 Here, we report the effect of the CYP3A4*20 frameshift allele in two Spanish liver transplant patients treated with tacrolimus. Tacrolimus 116-126 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 34-40 29256966-10 2018 CONCLUSION: This first description of CYP3A4*20 null genotype in liver-transplanted patients, supports the relevance of CYP3A genotyping in tacrolimus therapy. Tacrolimus 140-150 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 38-44 29256966-10 2018 CONCLUSION: This first description of CYP3A4*20 null genotype in liver-transplanted patients, supports the relevance of CYP3A genotyping in tacrolimus therapy. Tacrolimus 140-150 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 38-43 30251601-0 2018 Influence of CYP3A and ABCB1 Single Nucleotide Polymorphisms on the Pharmacokinetics/Pharmacodynamics of Tacrolimus in Pediatric Patients. Tacrolimus 105-115 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 13-18 30251601-4 2018 This article focuses on the effects of ABCB1 and CYP3A SNPs on tacrolimus in children who are undergoing organ transplantations. Tacrolimus 63-73 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 49-54 27378609-0 2017 Effect of ABCB1 diplotype on tacrolimus disposition in renal recipients depends on CYP3A5 and CYP3A4 genotype. Tacrolimus 29-39 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 94-100 29801578-4 2018 For calcineurin inhibitors like cyclosporine and in particular tacrolimus however, cytochrome P450 3A4 and 3A5 variants were found to significantly affect the pharmacokinetics. Tacrolimus 63-73 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 83-102 30156148-12 2018 Additionally, genetic CYP3A4 variation (e.g., CYP3A4*22) is also associated with interindividual variability of exposure level to tacrolimus. Tacrolimus 130-140 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 22-28 30156148-12 2018 Additionally, genetic CYP3A4 variation (e.g., CYP3A4*22) is also associated with interindividual variability of exposure level to tacrolimus. Tacrolimus 130-140 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 46-52 28603840-1 2017 AIMS: The CYP3A metric 4beta-hydroxycholesterol (4betaOHC) has been shown to correlate with tacrolimus steady-state apparent oral clearance (CL/F). Tacrolimus 92-102 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 10-15 28945481-7 2017 RESULTS: The alleles CYP3A5*3 and CYP3A4*18B were significantly associated with dose-adjusted tacrolimus blood trough concentrations and had a strong time-genotype interaction with tacrolimus pharmacokinetics. Tacrolimus 94-104 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 34-40 28945481-7 2017 RESULTS: The alleles CYP3A5*3 and CYP3A4*18B were significantly associated with dose-adjusted tacrolimus blood trough concentrations and had a strong time-genotype interaction with tacrolimus pharmacokinetics. Tacrolimus 181-191 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 34-40 28945481-10 2017 Thus, genotyping of the CYP3A4 and CYP3A5 genes should be considered with respect to determining tacrolimus dose regimens during the post-transplantation period. Tacrolimus 97-107 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 24-30 28621555-4 2017 The model of donors" CYP3A5 rs776746 and recipients" CYP3A4 rs2242480 could predict tacrolimus metabolism at week 1 and the model of donors" CYP3A5 rs776746, recipients" CYP3A4 rs2242480, recipients" SLC28A3 rs7853758 and hemoglobin could predict tacrolimus disposition at weeks 2, 3 and 4. Tacrolimus 84-94 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-59 28722255-3 2017 All of these agents are inhibitors of cytochrome P450 3A4, which plays a key role in metabolizing immunosuppressant drugs such as cyclosporine, tacrolimus, and sirolimus. Tacrolimus 144-154 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 38-57 28704257-0 2017 The combination of CYP3A4*22 and CYP3A5*3 single-nucleotide polymorphisms determines tacrolimus dose requirement after kidney transplantation. Tacrolimus 85-95 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 19-25 28621555-4 2017 The model of donors" CYP3A5 rs776746 and recipients" CYP3A4 rs2242480 could predict tacrolimus metabolism at week 1 and the model of donors" CYP3A5 rs776746, recipients" CYP3A4 rs2242480, recipients" SLC28A3 rs7853758 and hemoglobin could predict tacrolimus disposition at weeks 2, 3 and 4. Tacrolimus 84-94 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 170-176 28050888-1 2017 BACKGROUND: Single nucleotide polymorphisms (SNPs) in the CYP3A5 and CYP3A4 genes have been reported to be an important cause of variability in the pharmacokinetics of tacrolimus in renal transplant patients. Tacrolimus 168-178 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 69-75 28050888-8 2017 CONCLUSIONS: Tacrolimus disposition in renal transplant recipients was described using a new population pharmacokinetic model that included the CYP3A5*3 and CYP3A4*22 genotype, age, and hematocrit. Tacrolimus 13-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 157-163 28050888-0 2017 A New CYP3A5*3 and CYP3A4*22 Cluster Influencing Tacrolimus Target Concentrations: A Population Approach. Tacrolimus 49-59 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 19-25 29050276-0 2017 A new donors" CYP3A5 and recipients" CYP3A4 cluster predicting tacrolimus disposition, and new-onset hypertension in Chinese liver transplant patients. Tacrolimus 63-73 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 37-43 28374426-0 2017 Response to: "Response to: Bodyweight-adjustments introduce significant correlations between CYP3A metrics and tacrolimus clearance". Tacrolimus 111-121 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 93-98 28146606-2 2017 Tacrolimus dosing is challenged by considerable pharmacokinetic variability, both between patients and over time after transplantation, partly due to variability in cytochrome P450 3A (CYP3A) activity. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 165-183 28146606-2 2017 Tacrolimus dosing is challenged by considerable pharmacokinetic variability, both between patients and over time after transplantation, partly due to variability in cytochrome P450 3A (CYP3A) activity. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 185-190 28146606-3 2017 The aim of this study was to assess the value of the endogenous CYP3A marker 4beta-hydroxycholesterol (4betaOHC) for tacrolimus dose individualization early after kidney transplantation. Tacrolimus 117-127 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 64-69 28642710-0 2017 Tacrolimus Updated Guidelines through popPK Modeling: How to Benefit More from CYP3A Pre-emptive Genotyping Prior to Kidney Transplantation. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 79-84 28642710-4 2017 The integration of CYP3A4 and CY3A5 genotype in tacrolimus population-based PK (PopPK) modeling approaches has been proven to accurately predict the dose requirement to reach the therapeutic window. Tacrolimus 48-58 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 19-25 28642710-10 2017 Our model estimated that tacrolimus concentrations were 33% IC95%[20-26%], 41% IC95%[36-45%] lower in CYP3A IM and EM when compared to PM, respectively. Tacrolimus 25-35 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 102-107 28324194-8 2017 Since the blood concentration of tacrolimus in patients with CYP3A5*3/*3 varies depending on sex and age, these factors should be considered when studying the difference of sex in CYP3A. Tacrolimus 33-43 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 61-66 28008657-0 2017 Bodyweight-adjustments introduce significant correlations between CYP3A metrics and tacrolimus clearance. Tacrolimus 84-94 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 66-71 28044353-2 2017 METHODS: The contribution of the CYP3A4/5 genotype in paediatric liver transplant recipients and donors to the tacrolimus blood trough concentrations (C0 ) and the tacrolimus concentration/weight-adjusted dose ratio on day 1 was evaluated in 67 liver-transplanted children: 33 boys and 34 girls, mean age 4.5 years. Tacrolimus 111-121 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 33-39 28229376-1 2017 INTRODUCTION: Tacrolimus is a calcineurin inhibitor used as an immunosuppressant drug in solid organ transplantation, and is mainly metabolized by cytochrome P450 (CYP) 3A4 and CYP3A5. Tacrolimus 14-24 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 147-172 28168728-0 2017 Response to: "Bodyweight-adjustments introduce significant correlations between CYP3A metrics and tacrolimus clearance". Tacrolimus 98-108 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 80-85 28229376-3 2017 Variants in the genes PPARA, POR and CYP3A4 have recently been shown to influence tacrolimus metabolism. Tacrolimus 82-92 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 37-43 28229376-5 2017 In the present study, we investigated a potential association between CYP3A5*3, PPARA c.209-1003G>A, POR*28 and CYP3A4*22 and dose-adjusted tacrolimus trough concentrations in a primarily corticosteroid-free (>85%) population of Danish pediatric and adult kidney transplant recipients. Tacrolimus 143-153 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 115-121 27890698-7 2017 Thus, inhibition of CYP3A4 is presumably the underlying reason for the observed increase in the concentrations of the CYP3A4 substrate tacrolimus in the patient. Tacrolimus 135-145 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 20-26 27822915-4 2017 Multiple regression analysis showed that concomitant use of oral itraconazole or voriconazole significantly increased the (C/Dpo)/(C/Div) of tacrolimus (p = 0.002), probably owing to the inhibition of enterohepatic cytochrome P450 3A4. Tacrolimus 141-151 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 215-234 28219593-2 2017 Tacrolimus, an immunosuppressant that protects against organ rejection in transplant recipients, not only is mainly metabolized by CYP3A enzymes but also has a narrow therapeutic range. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 131-136 27890698-7 2017 Thus, inhibition of CYP3A4 is presumably the underlying reason for the observed increase in the concentrations of the CYP3A4 substrate tacrolimus in the patient. Tacrolimus 135-145 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 118-124 27310200-8 2016 Cyclosporine predominantly inhibited CYP3A4 (half maximal inhibitory concentration = 0.71 microM) rather than CYP3A5 (>5 microM), whereas tacrolimus showed similar inhibition for CYP3A4 (0.29 microM) and CYP3A5 (0.41 microM). Tacrolimus 141-151 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 182-188 28655393-0 2017 The role of single nucleotide polymorphisms of CYP3A and ABCB1 on tacrolimus predose concentration in kidney transplant recipients. Tacrolimus 66-76 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 47-52 28655393-8 2017 On the other hand, less than 1% of our transplant recipients possess the <italic>CYP3A</italic> genotype, which requires high daily tacrolimus dose. Tacrolimus 144-154 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 87-92 27399255-10 2016 Everolimus and tacrolimus are two immunosuppressive drugs metabolized by CYP3A4. Tacrolimus 15-25 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 73-79 27314545-2 2016 We sought to determine the singular and combined impact of CYP3A4*22 and CYP3A5*3 variants on tacrolimus drug disposition in adult heart transplant recipients. Tacrolimus 94-104 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 59-65 27314545-8 2016 When combined CYP3A genotypes were evaluated, tacrolimus C0 /D was 1.8-fold lower in EMs vs IMs (P<.001) and EMs vs PMs (P=.001). Tacrolimus 46-56 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 14-19 27314545-10 2016 CONCLUSION: Combined CYP3A genotype was associated with tacrolimus drug disposition in adult heart transplant recipients, but the effect was largely driven by CYP3A5*3. Tacrolimus 56-66 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 21-26 26271661-2 2015 CYP3A5*3, CYP3A4*1B and CYP3A4*22 alleles of liver grafts may explain about one third of the inter-individual differences in pharmacokinetics of ciclosporin and tacrolimus in recipients. Tacrolimus 161-171 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 10-16 27225724-0 2016 Effects of Genetic Polymorphism in CYP3A4 and CYP3A5 Genes on Tacrolimus Dose Among Kidney Transplant Recipients. Tacrolimus 62-72 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 35-41 27225724-1 2016 INTRODUCTION: This study aimed to evaluate the effects of single nucleotide polymorphisms CYP3A4*1B and CYP3A5*3 on tacrolimus dose requirement among kidney transplant recipients. Tacrolimus 116-126 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 90-96 27225724-4 2016 RESULTS: The median tacrolimus dose was significantly lower in the CYP3A4*1/*1 carriers (0.06 mg/kg/d; range, 0.007 mg/kg/d to 0.17 mg/kg/d) as compared to the CYP3A4*1B/*1B carriers (0.1 mg/kg/d; range, 0.03 mg/kg/d to 0.22 mg/kg/d; P = .001). Tacrolimus 20-30 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 67-73 27225724-4 2016 RESULTS: The median tacrolimus dose was significantly lower in the CYP3A4*1/*1 carriers (0.06 mg/kg/d; range, 0.007 mg/kg/d to 0.17 mg/kg/d) as compared to the CYP3A4*1B/*1B carriers (0.1 mg/kg/d; range, 0.03 mg/kg/d to 0.22 mg/kg/d; P = .001). Tacrolimus 20-30 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 160-166 27225724-7 2016 Moreover, we found a correlation between genetic variations in CYP3A4 and CYP3A5 enzymes and tacrolimus blood levels among our kidney transplant recipients. Tacrolimus 93-103 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 63-69 26924289-0 2016 Prediction of tacrolimus metabolism and dosage requirements based on CYP3A4 phenotype and CYP3A5(*)3 genotype in Chinese renal transplant recipients. Tacrolimus 14-24 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 69-75 26924289-8 2016 CONCLUSION: This study provides the equations to predict tacrolimus metabolism and dosage requirements based on the endogenous CYP3A4 phenotype, CYP3A5(*)3 genotype and other non-genetic variables. Tacrolimus 57-67 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 127-133 26433738-4 2016 Dose-adjusted tacrolimus concentration was used as a surrogate marker of CYP3A4 activity. Tacrolimus 14-24 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 73-79 26433738-9 2016 Liver transplant recipients with impaired renal function or a low dose-adjusted tacrolimus concentration suggesting a high CYP3A4 are at risk of low 1,25(OH)2D3 concentrations. Tacrolimus 80-90 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 123-129 26239045-6 2016 These results demonstrate that CYP2C19 genotypes influenced the exposure of tacrolimus when coadministered with voriconazole, although tacrolimus is mainly metabolized by CYP3A. Tacrolimus 135-145 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 171-176 26521259-4 2016 The primary objective of this study was to investigate the effect of CYP3A4*22 and CYP3A5*3 of both donor and recipient on once daily tacrolimus pharmacokinetics. Tacrolimus 134-144 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 69-75 26651976-1 2016 BACKGROUND: The contribution of the CYP3A5 enzyme to the metabolism of clinically used drugs has been established only for a few CYP3A substrates, such as the immunosuppressant tacrolimus, while for drugs used in the field of psychiatry its role is still vague. Tacrolimus 177-187 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 36-41 26271661-2 2015 CYP3A5*3, CYP3A4*1B and CYP3A4*22 alleles of liver grafts may explain about one third of the inter-individual differences in pharmacokinetics of ciclosporin and tacrolimus in recipients. Tacrolimus 161-171 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 24-30 26114223-0 2015 Progressive decline in tacrolimus clearance after renal transplantation is partially explained by decreasing CYP3A4 activity and increasing haematocrit. Tacrolimus 23-33 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 109-115 26615671-1 2015 AIM: The present study investigated in Tunisian renal transplant patients, genetic polymorphisms of CYP3A4 -392A>G and CYP3A5 6986A>G and their influence on tacrolimus (Tac) pharmacokinetics during early and late post-transplant (PT) phases and established customized ranges of Tac doses matching the C0 target levels according to CYP3A4 and CYP3A5 genotype combination and the PT phase. Tacrolimus 163-173 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 100-106 26615671-1 2015 AIM: The present study investigated in Tunisian renal transplant patients, genetic polymorphisms of CYP3A4 -392A>G and CYP3A5 6986A>G and their influence on tacrolimus (Tac) pharmacokinetics during early and late post-transplant (PT) phases and established customized ranges of Tac doses matching the C0 target levels according to CYP3A4 and CYP3A5 genotype combination and the PT phase. Tacrolimus 163-173 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 337-343 26184414-7 2015 CONCLUSIONS: In CYP3A5*3/*3 patients, because the metabolic pathway for tacrolimus occurs only through CYP3A4, the combination with ITCZ seems to lead to a higher risk of acute renal dysfunction. Tacrolimus 72-82 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 103-109 26770526-2 2015 The genetic polymorphisms of CYP3A4, CYP3A5 and MDR1 in 216 RT patients were detected by PCR-RFLP, the genetic and clinical factors and blood concentration/dose x body weight (C/D) values of tacrolimus were performed the single factor correlation analysis, and established the dose prediction algorithm of tacrolimus by stepwise multiple regression analysis. Tacrolimus 191-201 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 29-35 26770526-2 2015 The genetic polymorphisms of CYP3A4, CYP3A5 and MDR1 in 216 RT patients were detected by PCR-RFLP, the genetic and clinical factors and blood concentration/dose x body weight (C/D) values of tacrolimus were performed the single factor correlation analysis, and established the dose prediction algorithm of tacrolimus by stepwise multiple regression analysis. Tacrolimus 306-316 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 29-35 26114223-5 2015 In mixed model analysis, decreasing CYP3A4 activity, measured by apparent oral MDZ clearance (924 +- 443 ml min(-1) at day 7 vs. 730 +- 344 ml min(-1) at month 1; P < 0.001), explained 55.4% of the decline in tacrolimus clearance in the first month. Tacrolimus 212-222 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 36-42 26114223-9 2015 CONCLUSIONS: The maturation of tacrolimus disposition in the first year after renal transplantation observed in CYP3A5*3/*3 homozygous patients can partly be explained by a (steroid tapering-related) decline in CYP3A4 activity and a progressive increase in haematocrit. Tacrolimus 31-41 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 211-217 26334901-6 2015 When compared with the wild-type genotype, the variant genotypes rs5767743 and rs5767700 correlated with significantly increased PPARalpha and CYP3A4 mRNA expression and lower tacrolimus trough concentration/dose ratios (P < 0.05 for all).Donor PPARalpha gene polymorphisms influence the susceptibility to metabolic disorders following LT and may also be associated with a fasten tacrolimus metabolism because of elevated CYP3A4 expression. Tacrolimus 176-186 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 143-149 26227094-5 2015 RESULTS: The significant influences of CYP3A5*3, CYP3A4*1G, and POR*28 polymorphisms on tacrolimus dose-adjusted trough concentrations (C0/D) were observed in 83 renal recipients. Tacrolimus 88-98 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 49-55 26334901-6 2015 When compared with the wild-type genotype, the variant genotypes rs5767743 and rs5767700 correlated with significantly increased PPARalpha and CYP3A4 mRNA expression and lower tacrolimus trough concentration/dose ratios (P < 0.05 for all).Donor PPARalpha gene polymorphisms influence the susceptibility to metabolic disorders following LT and may also be associated with a fasten tacrolimus metabolism because of elevated CYP3A4 expression. Tacrolimus 176-186 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 425-431 26334901-6 2015 When compared with the wild-type genotype, the variant genotypes rs5767743 and rs5767700 correlated with significantly increased PPARalpha and CYP3A4 mRNA expression and lower tacrolimus trough concentration/dose ratios (P < 0.05 for all).Donor PPARalpha gene polymorphisms influence the susceptibility to metabolic disorders following LT and may also be associated with a fasten tacrolimus metabolism because of elevated CYP3A4 expression. Tacrolimus 383-393 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 143-149 26334901-6 2015 When compared with the wild-type genotype, the variant genotypes rs5767743 and rs5767700 correlated with significantly increased PPARalpha and CYP3A4 mRNA expression and lower tacrolimus trough concentration/dose ratios (P < 0.05 for all).Donor PPARalpha gene polymorphisms influence the susceptibility to metabolic disorders following LT and may also be associated with a fasten tacrolimus metabolism because of elevated CYP3A4 expression. Tacrolimus 383-393 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 425-431 25881619-1 2015 OBJECTIVES: Emerging data suggest that the combination of tacrolimus and the CCR5 antagonist maraviroc, both cytochrome P450-3A4 substrates, may be effective in preventing graft-versus-host disease in patients undergoing allogeneic HSCT. Tacrolimus 58-68 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 109-128 25600613-6 2015 The relationship of the IC50 values of 11 inhibitors between tacrolimus and typical CYP3A substrates (midazolam and testosterone) was also analysed. Tacrolimus 61-71 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 84-89 25600613-7 2015 A strong correlation was found between the IC50 values of tacrolimus and typical CYP3A substrates (r(2) >= 0.85). Tacrolimus 58-68 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 81-86 25600613-14 2015 within an approximately 2-fold range of observed values) the effect of CYP3A inhibitors on the tacrolimus AUCp.o. Tacrolimus 95-105 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 71-76 25894154-1 2015 OBJECTIVES: Tacrolimus is the cornerstone for immunosuppression in renal transplant and is metabolized by the cytochrome P 450 3A (CYP3A) subfamily of enzymes in the liver and small intestine. Tacrolimus 12-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 110-129 26039043-0 2015 Effects of the CYP3A4*1B Genetic Polymorphism on the Pharmacokinetics of Tacrolimus in Adult Renal Transplant Recipients: A Meta-Analysis. Tacrolimus 73-83 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 15-21 26039043-1 2015 BACKGROUND AND OBJECTIVE: The association between the CYP3A4*1B single nucleotide polymorphism (SNP) and tacrolimus pharmacokinetics in different studies is controversial. Tacrolimus 105-115 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 54-60 26039043-2 2015 Therefore, a meta-analysis was employed to evaluate the correlation between the CYP3A4*1B genetic polymorphism and tacrolimus pharmacokinetics at different post-transplantation times in adult renal transplant recipients. Tacrolimus 115-125 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 80-86 26039043-7 2015 In light of the heterogeneity, the analysis was repeated after removing the only study in an Indian population, and CYP3A4*1/*1 European recipients (mostly Caucasian) required a lower weight-adjusted tacrolimus daily dose within the first year post-transplantation. Tacrolimus 200-210 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 116-122 26039043-8 2015 The tacrolimus trough concentration/weight-adjusted tacrolimus daily dose ratio (C0/Dose ratio) was significantly higher in CYP3A4*1/*1 recipients than in CYP3A4*1B carriers at 6 months (WMD 52.588; 95% CI 22.387 ~ 82.789) and 12 months (WMD 62.219; 95% CI 14.218 ~ 110.221) post-transplantation. Tacrolimus 4-14 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 124-130 26039043-8 2015 The tacrolimus trough concentration/weight-adjusted tacrolimus daily dose ratio (C0/Dose ratio) was significantly higher in CYP3A4*1/*1 recipients than in CYP3A4*1B carriers at 6 months (WMD 52.588; 95% CI 22.387 ~ 82.789) and 12 months (WMD 62.219; 95% CI 14.218 ~ 110.221) post-transplantation. Tacrolimus 4-14 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 155-161 26039043-8 2015 The tacrolimus trough concentration/weight-adjusted tacrolimus daily dose ratio (C0/Dose ratio) was significantly higher in CYP3A4*1/*1 recipients than in CYP3A4*1B carriers at 6 months (WMD 52.588; 95% CI 22.387 ~ 82.789) and 12 months (WMD 62.219; 95% CI 14.218 ~ 110.221) post-transplantation. Tacrolimus 52-62 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 124-130 26039043-10 2015 CONCLUSION: Based on our meta-analysis, the CYP3A4*1B genetic polymorphism affects tacrolimus dose requirements and tacrolimus trough concentration/weight-adjusted tacrolimus daily dose ratio within the first year post-transplantation in adult renal transplant recipients, especially in European recipients (mostly Caucasian). Tacrolimus 83-93 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 44-50 26039043-10 2015 CONCLUSION: Based on our meta-analysis, the CYP3A4*1B genetic polymorphism affects tacrolimus dose requirements and tacrolimus trough concentration/weight-adjusted tacrolimus daily dose ratio within the first year post-transplantation in adult renal transplant recipients, especially in European recipients (mostly Caucasian). Tacrolimus 116-126 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 44-50 26039043-10 2015 CONCLUSION: Based on our meta-analysis, the CYP3A4*1B genetic polymorphism affects tacrolimus dose requirements and tacrolimus trough concentration/weight-adjusted tacrolimus daily dose ratio within the first year post-transplantation in adult renal transplant recipients, especially in European recipients (mostly Caucasian). Tacrolimus 116-126 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 44-50 25271728-4 2015 Recently, CYP3A4*22 was reported to additionally affect tacrolimus pharmacokinetics (PK). Tacrolimus 56-66 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 10-16 26067485-2 2015 PATIENTS & METHODS: We studied genetic correlates of tacrolimus trough concentrations with POR*28, CYP3A4*22 and ABCC2 haplotypes in a large, ethnically diverse kidney transplant cohort (n = 2008). Tacrolimus 57-67 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 103-109 25894154-1 2015 OBJECTIVES: Tacrolimus is the cornerstone for immunosuppression in renal transplant and is metabolized by the cytochrome P 450 3A (CYP3A) subfamily of enzymes in the liver and small intestine. Tacrolimus 12-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 131-136 25287072-0 2015 The CYP3A4*22 C>T single nucleotide polymorphism is associated with reduced midazolam and tacrolimus clearance in stable renal allograft recipients. Tacrolimus 93-103 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 4-10 25287072-1 2015 Tacrolimus, a dual substrate of CYP3A4 and CYP3A5 has a narrow therapeutic index and is characterized by high between-subject variability in oral bioavailability. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 32-38 25588704-0 2015 Kidney transplant recipients carrying the CYP3A4*22 allelic variant have reduced tacrolimus clearance and often reach supratherapeutic tacrolimus concentrations. Tacrolimus 81-91 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 42-48 25588704-0 2015 Kidney transplant recipients carrying the CYP3A4*22 allelic variant have reduced tacrolimus clearance and often reach supratherapeutic tacrolimus concentrations. Tacrolimus 135-145 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 42-48 25561870-9 2014 Therefore, using Ferula asafetida with CYP3A4 drug substrates should be cautioned especially those with narrow therapeutic index such as cyclosporine, tacrolimus and carbamazepine. Tacrolimus 151-161 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 39-45 25968921-1 2015 Tacrolimus is a calcineurin inhibitor primarily metabolized by CYP3A4 and secondarily by CYP3A5. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 63-69 25968921-8 2015 Increase of tacrolimus trough concentrations is due to the inhibition of CYP3A4. Tacrolimus 12-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 73-79 25877445-0 2015 Reversible, time-dependent inhibition of CYP3A-mediated metabolism of midazolam and tacrolimus by telaprevir in human liver microsomes. Tacrolimus 84-94 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 41-46 25877445-3 2015 METHODS: We performed a static mechanistic DDI prediction to evaluate whether previously reported competitive inhibition of CYP3A by telaprevir and its diastereomeric metabolite - VRT-127394 is sufficient to explain the remarkable reduction in oral clearance observed with oral midazolam and tacrolimus. Tacrolimus 292-302 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 124-129 25916520-0 2015 Relationship between mRNA expression levels of CYP3A4, CYP3A5 and SXR in peripheral mononuclear blood cells and aging in young kidney transplant recipients under tacrolimus treatment. Tacrolimus 162-172 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 47-53 25916520-5 2015 PATIENTS & METHODS: The correlation between the levels of mRNA specific for key enzymes SXR, CYP3A and ABCB1 involved in the metabolism of tacrolimus was evaluated in PBMCs obtained from a selected population of 29 young kidney transplant recipients. Tacrolimus 143-153 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 97-102 25916520-8 2015 tacrolimus-normalized daily dose was strongly correlated with patient"s age and multivariable regression indicates the CYP3A4-specific mRNA as the sole independent variable influencing tacrolimus concentration-to-dose ratio. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 119-125 25916520-8 2015 tacrolimus-normalized daily dose was strongly correlated with patient"s age and multivariable regression indicates the CYP3A4-specific mRNA as the sole independent variable influencing tacrolimus concentration-to-dose ratio. Tacrolimus 185-195 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 119-125 25322286-6 2014 Multivariate analyses identified the CYP3A5*1/POR*28/CYP3A4*22 genotype combination as the single strongest determinant of tacrolimus dose requirements throughout the first year, explaining between 24-40% of its variability, whereas recipient age, hematocrit, and delayed graft function were additional nongenetic determinants of tacrolimus dose. Tacrolimus 123-133 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-59 25322286-7 2014 CONCLUSION: Combining the CYP3A5*1, POR*28 and CYP3A4*22 genotypes allows partial differentiation of early tacrolimus dose requirements and the time to reach therapeutic target concentrations after transplantation, but without obvious clinical implications. Tacrolimus 107-117 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 47-53 24739669-3 2014 We thus assessed the role of genetic variation in CYP3A4, CYP3A5, POR, NR1I2, and ABCB1 acting jointly in immunosuppressive drug pathways in tacrolimus (TAC) and ciclosporin (CSA) dose requirement in HTx recipients. Tacrolimus 141-151 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 50-56 26228923-4 2015 CYP3A4*1G, MDR1 1236-2677-3435 diplotype and NR1I2 -25385C > T explained 21.4% of variability of tacrolimus C0D7/D in CYP3A5 nonexpressers. Tacrolimus 100-110 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 26228923-6 2015 Genotyping of CYP3A4/MDR1/NR1I2 polymorphisms may be helpful for better guiding tacrolimus dosing in CYP3A5 nonexpressers. Tacrolimus 80-90 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 14-20 25141896-6 2014 Time post-transplantation, recipient age, donor CYP3A5 and CYP3A4 genotypes and fluconazole administration significantly influenced tacrolimus apparent clearance while bodyweight influenced volume of distribution. Tacrolimus 132-142 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 59-65 25125128-1 2014 BACKGROUND: Tacrolimus is a CYP3A4 inhibitor and can alter colchicine metabolism. Tacrolimus 12-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 28-34 24658827-1 2014 PURPOSE: Tacrolimus (Tac) and cyclosporine (CsA) are mainly metabolized by CYP3A4 and CYP3A5. Tacrolimus 9-19 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 75-81 28346678-0 2014 CORRIGENDUM: Identification and Characterization of a Defective CYP3A4 Genotype in a Kidney Transplant Patient With Severely Diminished Tacrolimus Clearance. Tacrolimus 136-146 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 64-70 24522145-5 2014 CYP3A4*22 carriers showed a significant lower clearance for cyclosporine (-15%), and a trend was observed for everolimus (-7%) and tacrolimus (-16%). Tacrolimus 131-141 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 24526611-3 2014 A physiologically based pharmacokinetic (PBPK) model of tacrolimus was proposed, taking into account the body weight, the proportion of fat (P(fat)), hematocrit, lipid fraction of organs, typical intrinsic clearance (CLi(typ)), CYP3A5 genotype of liver donor, plasma unbound fraction of tacrolimus (fu(p)), and concomitant drugs (CYP3A4 inhibitors). Tacrolimus 56-66 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 330-336 24462213-7 2014 Metabolism study in the human recombinant CYP 3A showed that these lignans had higher affinity to CYP3A than that of FK506, and thus had a stronger CYP3A-mediated metabolism. Tacrolimus 117-122 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 42-48 24462213-7 2014 Metabolism study in the human recombinant CYP 3A showed that these lignans had higher affinity to CYP3A than that of FK506, and thus had a stronger CYP3A-mediated metabolism. Tacrolimus 117-122 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 148-153 24462213-8 2014 It was concluded that the blood concentrations of these lignans were decreased and their CYP3A-mediated metabolisms were increased in the presence of FK506 since these lignans had higher affinity to CYP3A. Tacrolimus 150-155 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 89-94 24462213-8 2014 It was concluded that the blood concentrations of these lignans were decreased and their CYP3A-mediated metabolisms were increased in the presence of FK506 since these lignans had higher affinity to CYP3A. Tacrolimus 150-155 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 199-204 24126681-0 2014 Identification and characterization of a defective CYP3A4 genotype in a kidney transplant patient with severely diminished tacrolimus clearance. Tacrolimus 123-133 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 51-57 24126681-7 2014 In addition, the patient harbored inactive CYP3A5*3, resulting in loss of function of the entire CYP3A locus, explaining the deteriorated tacrolimus clearance. Tacrolimus 138-148 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 43-48 24444408-0 2014 CYP3A5 and CYP3A4, but not ABCB1 polymorphisms affect tacrolimus dose-adjusted trough concentrations in kidney transplant recipients. Tacrolimus 54-64 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 11-17 24249597-10 2014 Individuals carrying the CYP3A4*22 T-variant allele have a lower tacrolimus dose requirement than individuals with the CYP3A4*22 CC genotype and this effect appears to be independent of CYP3A5 genotype status. Tacrolimus 65-75 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 25-31 24249597-10 2014 Individuals carrying the CYP3A4*22 T-variant allele have a lower tacrolimus dose requirement than individuals with the CYP3A4*22 CC genotype and this effect appears to be independent of CYP3A5 genotype status. Tacrolimus 65-75 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 119-125 24061445-2 2014 Both CYP3A5 and CYP3A4 are involved in the metabolism of calcineurin inhibitors and recent data show that POR*28 may explain part of the variability observed in tacrolimus (Tac) pharmacokinetics. Tacrolimus 161-171 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 16-22 24369269-3 2014 Before initiation of triple therapy, all patients switched from tacrolimus to cyclosporine, which has a lower inhibitory effect on CYP3A4 and CYP3A5 than tacrolimus. Tacrolimus 64-74 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 131-137 24033383-1 2014 BACKGROUND AND AIM: The pharmacokinetics of tacrolimus (Tac) differ among individuals, and genetic polymorphisms of cytochrome P-450 (CYP) 3A4, CYP3A5, and ABCB1 are thought to be involved. Tacrolimus 44-54 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 116-142 24052064-0 2013 Impact of CYP3A4*22 allele on tacrolimus pharmacokinetics in early period after renal transplantation: toward updated genotype-based dosage guidelines. Tacrolimus 30-40 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 10-16 24656020-1 2014 BACKGROUND: The bioavailability of oral tacrolimus is influenced by enterocyte metabolism, which involves CYP3A and P-glycoprotein. Tacrolimus 40-50 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 106-111 24052064-1 2013 BACKGROUND: Tacrolimus (Tac) metabolism is mainly mediated by the cytochrome P450 3A (CYP3A) subfamily. Tacrolimus 12-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 66-84 24052064-1 2013 BACKGROUND: Tacrolimus (Tac) metabolism is mainly mediated by the cytochrome P450 3A (CYP3A) subfamily. Tacrolimus 12-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 86-91 23574377-1 2013 WHAT IS KNOWN AND OBJECTIVE: Tacrolimus has a narrow therapeutic index and shows large interindividual variations in pharmacokinetics, which may be partly explained by genetic variability in metabolic enzymes of the cytochrome P450 (mainly CYP3A4 and CYP3A5) and transport P-glycoprotein (encoded by the ABCB1 gene). Tacrolimus 29-39 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 240-246 24024898-1 2013 BACKGROUND & AIM: In vitro studies have identified both midazolam and tacrolimus as dual CYP3A4 and CYP3A5 substrates. Tacrolimus 74-84 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 93-99 23778326-0 2013 A search for new CYP3A4 variants as determinants of tacrolimus dose requirements in renal-transplanted patients. Tacrolimus 52-62 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 17-23 23778326-1 2013 The CYP3A5*3 and CYP3A4*1B alleles have been related with tacrolimus (Tac) dose requirements. Tacrolimus 58-68 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 17-23 23278282-8 2013 CYP3A4*1B carriers and CYP3A5 expressers, independently or when assessed as a combined CYP3A4-3A5 genotype, had significantly lower dose-normalized pre-dose (C0/dose) and 2-hour post-dose (C2/dose) concentrations of tacrolimus and metabolites. Tacrolimus 216-226 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-9 23837477-0 2013 CYP3A4*22 and CYP3A combined genotypes both correlate with tacrolimus disposition in pediatric heart transplant recipients. Tacrolimus 59-69 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 23837477-0 2013 CYP3A4*22 and CYP3A combined genotypes both correlate with tacrolimus disposition in pediatric heart transplant recipients. Tacrolimus 59-69 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-5 23837477-1 2013 BACKGROUND: Tacrolimus metabolism depends on CYP3A4 and CYP3A5. Tacrolimus 12-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 45-51 23837477-2 2013 We aimed to determine the relationship between the CYP3A4*22 polymorphism and combined CYP3A genotypes with tacrolimus disposition in pediatric heart transplant recipients. Tacrolimus 108-118 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 51-57 23837477-2 2013 We aimed to determine the relationship between the CYP3A4*22 polymorphism and combined CYP3A genotypes with tacrolimus disposition in pediatric heart transplant recipients. Tacrolimus 108-118 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 51-56 23837477-6 2013 RESULTS: CYP3A4*22 carriers needed 30% less tacrolimus (p = 0.016) to reach similar target concentrations compared with CYP3A4*1/*1 (n = 56) carriers. Tacrolimus 44-54 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 9-15 23837477-7 2013 Poor CYP3A metabolizers required 17% (p = 0.023) less tacrolimus than intermediate and 48% less (p < 0.0001) than extensive metabolizers. Tacrolimus 54-64 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 5-10 23837477-9 2013 CONCLUSION: Analysis of CYP3A4*22, either alone or in combination with CYP3A5*3, may help towards individualization of tacrolimus therapy in pediatric heart transplant patients. Tacrolimus 119-129 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 24-30 23278282-8 2013 CYP3A4*1B carriers and CYP3A5 expressers, independently or when assessed as a combined CYP3A4-3A5 genotype, had significantly lower dose-normalized pre-dose (C0/dose) and 2-hour post-dose (C2/dose) concentrations of tacrolimus and metabolites. Tacrolimus 216-226 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 23278282-11 2013 Genetic polymorphism of CYP3A5 or CYP3A4 influence tacrolimus or metabolites dose-normalized concentrations but not metabolite to parent concentration ratios. Tacrolimus 51-61 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 34-40 23557867-0 2013 CYP3A4/5 polymorphisms affect the blood level of cyclosporine and tacrolimus in Chinese renal transplant recipients. Tacrolimus 66-76 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 23163400-0 2013 The CYP3A4*22 allele affects the predictive value of a pharmacogenetic algorithm predicting tacrolimus predose concentrations. Tacrolimus 92-102 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 4-10 23557867-5 2013 RESULTS: Both CYP3A4*18B and CYP3A5*3 polymorphisms affected the tacrolimus dose-adjusted trough concentration (C0/D). Tacrolimus 65-75 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 14-20 23557867-10 2013 CONCLUSIONS: Genetic polymorphisms of CYP3A5*3 and CYP3A4*18B may be partly responsible in large interindividual variability of cyclosporine and tacrolimus blood levels in Chinese renal transplant patients during the first month after transplantation. Tacrolimus 145-155 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 51-57 23557867-11 2013 A patient carried combined genotype of CYP3A4*1/*1-CYP3A5* 3/*3 might require lower tacrolimus doses to achieve target concentration levels. Tacrolimus 84-94 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 39-45 23459029-10 2013 The findings suggest that CYP3A5*3 and CYP3A4*1G polymorphisms and hematocrit are determinant factors in the apparent clearance of tacrolimus. Tacrolimus 131-141 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 39-45 23481136-1 2013 BACKGROUND AND AIMS: Tacrolimus is a macrolide immunosuppressant used for prevention of allograft rejection in organ transplantation and metabolized in the liver and intestine by cytochrome P450 3A4 (CYP3A4) enzyme. Tacrolimus 21-31 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 179-198 23617933-2 2013 The CYP3A4*18, CYP3A5*3, and MDR1-3435 variant alleles are very important, particularly in tacrolimus metabolism in organ transplant rejection. Tacrolimus 91-101 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 4-10 23459029-2 2013 The aim of this study was to examine the association between tacrolimus pharmacokinetic variability and CYP3A4 and CYP3A5 genotypes by a population pharmacokinetic analysis based on routine drug monitoring data in adult renal transplant recipients. Tacrolimus 61-71 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 104-110 23459029-8 2013 The apparent clearance of tacrolimus was about two-fold higher in kidney transplant patients with higher enzymatic activity of CYP3A5*1 and CYP3A4*1G (with the CYP3A5*1/*1 or *1/*3 and CYP3A4*1/*1G or CYP3A4*1G/*1G) compared with those with lower enzymatic activity (CYP3A5*3/*3 and CYP3A4*1/*1). Tacrolimus 26-36 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 140-146 23459029-8 2013 The apparent clearance of tacrolimus was about two-fold higher in kidney transplant patients with higher enzymatic activity of CYP3A5*1 and CYP3A4*1G (with the CYP3A5*1/*1 or *1/*3 and CYP3A4*1/*1G or CYP3A4*1G/*1G) compared with those with lower enzymatic activity (CYP3A5*3/*3 and CYP3A4*1/*1). Tacrolimus 26-36 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 185-191 23459029-8 2013 The apparent clearance of tacrolimus was about two-fold higher in kidney transplant patients with higher enzymatic activity of CYP3A5*1 and CYP3A4*1G (with the CYP3A5*1/*1 or *1/*3 and CYP3A4*1/*1G or CYP3A4*1G/*1G) compared with those with lower enzymatic activity (CYP3A5*3/*3 and CYP3A4*1/*1). Tacrolimus 26-36 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 185-191 23459029-8 2013 The apparent clearance of tacrolimus was about two-fold higher in kidney transplant patients with higher enzymatic activity of CYP3A5*1 and CYP3A4*1G (with the CYP3A5*1/*1 or *1/*3 and CYP3A4*1/*1G or CYP3A4*1G/*1G) compared with those with lower enzymatic activity (CYP3A5*3/*3 and CYP3A4*1/*1). Tacrolimus 26-36 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 185-191 23459029-9 2013 CONCLUSION: This is the first study to extensively determine the effect of CYP3A4*1G and CYP3A5*3 genetic polymorphisms and hematocrit value on tacrolimus pharmacokinetics in Chinese renal transplant recipients. Tacrolimus 144-154 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 75-81 23947183-4 2013 Tacrolimus is mainly metabolized by cytochrome P450 isozymes, CYP3A4 and CYP3A5, expressed in the intestine as well as in the liver. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 62-68 23364483-0 2013 CYP3A and ABCB1 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of tacrolimus and its metabolites (M-I and M-III). Tacrolimus 86-96 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-5 23481136-1 2013 BACKGROUND AND AIMS: Tacrolimus is a macrolide immunosuppressant used for prevention of allograft rejection in organ transplantation and metabolized in the liver and intestine by cytochrome P450 3A4 (CYP3A4) enzyme. Tacrolimus 21-31 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 200-206 23175667-2 2013 Tacrolimus is mainly metabolized via CYP3A4/5, whereas CYP2C19 and CYP3A4/5 are responsible for omeprazole metabolism. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 37-45 23175667-2 2013 Tacrolimus is mainly metabolized via CYP3A4/5, whereas CYP2C19 and CYP3A4/5 are responsible for omeprazole metabolism. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 37-43 23107770-2 2013 The oral bioavailability of tacrolimus varies greatly between individuals and depends largely on the activity of both the cytochrome P450 3A (CYP3A) subfamily and P-glycoprotein (P-gp). Tacrolimus 28-38 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 122-140 23107770-2 2013 The oral bioavailability of tacrolimus varies greatly between individuals and depends largely on the activity of both the cytochrome P450 3A (CYP3A) subfamily and P-glycoprotein (P-gp). Tacrolimus 28-38 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 142-147 23107770-3 2013 The possible influence of single nucleotide polymorphisms (SNPs) of CYP3A subfamily and P-gp (MDR-1) in liver transplant recipients has recently been indicated as one of the most important variables affecting the pharmacokinetics of tacrolimus and the renal injury induced by tacrolimus. Tacrolimus 233-243 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 68-73 23107770-3 2013 The possible influence of single nucleotide polymorphisms (SNPs) of CYP3A subfamily and P-gp (MDR-1) in liver transplant recipients has recently been indicated as one of the most important variables affecting the pharmacokinetics of tacrolimus and the renal injury induced by tacrolimus. Tacrolimus 276-286 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 68-73 24189425-2 2013 The concentration/dose (C/D) ratio of tacrolimus in patients carrying graft liver with CYP3A4*1/*1 was significantly higher during 7 d after surgery than in that with CYP3A4*1/*1G (214 vs. 157 [ng/mL]/[mg/kg/day], p<0.01). Tacrolimus 38-48 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 87-93 24189425-8 2013 Thus, we elucidated that CYP3A4*1G genotype in the intestine was an important indicator of the pharmacokinetics of tacrolimus, whereas this genotype in the graft liver tended to influence the frequency of acute cellular rejection after transplantation. Tacrolimus 115-125 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 25-31 22993851-0 2012 [Effect of CYP3A4*18B, CYP3A5*3 gene polymorphism on dosage and concentration of tacrolimus in renal transplant patients]. Tacrolimus 81-91 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 11-17 23580932-4 2012 Tacrolimus has a large inter-/intra-patient variability in pharmacokinetics profile and a poor oral bioavailability because of its poor solubility, P-gp efflux, marked pre-systemic metabolism by CYP3A in the enterocytes and liver first pass effect. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 195-200 22871995-0 2012 In vivo CYP3A4 activity, CYP3A5 genotype, and hematocrit predict tacrolimus dose requirements and clearance in renal transplant patients. Tacrolimus 65-75 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 8-14 22871995-1 2012 Tacrolimus is metabolized by CYP3A4 and CYP3A5 and is characterized by a narrow therapeutic index and highly variable pharmacokinetics. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 29-35 22871995-3 2012 In vivo CYP3A4 activity and CYP3A5 genotype explain 56-59% of variability in tacrolimus dose requirements and clearance, contributing ~25 and 30%, respectively. Tacrolimus 77-87 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 8-14 22871995-5 2012 These data indicate that CYP3A4- and CYP3A5-mediated tacrolimus metabolisms are major determinants of tacrolimus disposition in vivo and explain a substantial part of the clinically observed high interindividual variability in tacrolimus pharmacokinetics. Tacrolimus 53-63 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 25-31 22871995-5 2012 These data indicate that CYP3A4- and CYP3A5-mediated tacrolimus metabolisms are major determinants of tacrolimus disposition in vivo and explain a substantial part of the clinically observed high interindividual variability in tacrolimus pharmacokinetics. Tacrolimus 102-112 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 25-31 22871995-5 2012 These data indicate that CYP3A4- and CYP3A5-mediated tacrolimus metabolisms are major determinants of tacrolimus disposition in vivo and explain a substantial part of the clinically observed high interindividual variability in tacrolimus pharmacokinetics. Tacrolimus 102-112 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 25-31 23252948-5 2013 A new CYP3A4 allele (CYP3A4*22; rs35599367 C>T in intron 6) with a frequency of 5-7% in the Caucasian population was recently discovered through its association with low hepatic CYP3A4 expression and CYP3A4 activity, and showing effects on statin, tacrolimus and cyclosporine metabolism. Tacrolimus 251-261 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 6-12 23252948-5 2013 A new CYP3A4 allele (CYP3A4*22; rs35599367 C>T in intron 6) with a frequency of 5-7% in the Caucasian population was recently discovered through its association with low hepatic CYP3A4 expression and CYP3A4 activity, and showing effects on statin, tacrolimus and cyclosporine metabolism. Tacrolimus 251-261 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 21-27 23252948-5 2013 A new CYP3A4 allele (CYP3A4*22; rs35599367 C>T in intron 6) with a frequency of 5-7% in the Caucasian population was recently discovered through its association with low hepatic CYP3A4 expression and CYP3A4 activity, and showing effects on statin, tacrolimus and cyclosporine metabolism. Tacrolimus 251-261 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 21-27 23252948-5 2013 A new CYP3A4 allele (CYP3A4*22; rs35599367 C>T in intron 6) with a frequency of 5-7% in the Caucasian population was recently discovered through its association with low hepatic CYP3A4 expression and CYP3A4 activity, and showing effects on statin, tacrolimus and cyclosporine metabolism. Tacrolimus 251-261 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 21-27 22576324-2 2012 Cyclosporine and tacrolimus are calcineurin inhibitor immunosuppressants used to prevent organ rejection after liver transplantation; both are substrates of CYP3A4. Tacrolimus 17-27 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 157-163 22993851-6 2012 While after the effects of CYP3A4*18B genotype were eliminated, the C/D" ratio of tacrolimus in patients with CYP3A5*1/*1 and *1/*3 genotype group was significantly lower than those with CYP3A5*3/*3 genotype groups (P < 0.01). Tacrolimus 82-92 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 27-33 22476221-6 2012 Both protease inhibitors can modify the levels of drugs metabolized by the CYP3A/4 pathway, and in posttransplant patients, the protease inhibitors increase the levels of cyclosporine and tacrolimus, with the magnitude of the drug-drug interactions varying with protease inhibitor and type of calcineurin inhibitor (CNI). Tacrolimus 188-198 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 75-82 22369694-6 2012 Our findings indicate that the CYP3A4*1B-CYP3A5*1 haplotype may have a more profound impact in tacrolimus PKs than the CYP3A5*1 allele. Tacrolimus 95-105 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 31-37 22205779-0 2012 Cyclosporine A- and tacrolimus-mediated inhibition of CYP3A4 and CYP3A5 in vitro. Tacrolimus 20-30 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 54-60 22491658-2 2012 Continuous intravenous nicardipine (CIVN), prescribed for posttransplant hypertension, inhibits tacrolimus metabolism by cytochrome P450 (CYP) 3A4 and could lead to tacrolimus overexposure in patients genetically lacking the alternative pathway for tacrolimus metabolism, CYP3A5. Tacrolimus 96-106 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 121-146 22310591-1 2012 BACKGROUND: Tacrolimus is a substrate of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), encoded by the CYP3A and ATP-binding cassette subfamily B member 1 (ABCB1) genes, respectively. Tacrolimus 12-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 41-59 22108237-9 2012 RESULTS: In analyses, which adjusted for race and other clinical factors, we replicated the association of tacrolimus blood concentration to dose ratio with CYP3A5 rs776746 (P=7.15x10), and identified associations with nine variants in linkage disequilibrium with rs776746, including eight CYP3A4 variants. Tacrolimus 107-117 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 290-296 22310591-1 2012 BACKGROUND: Tacrolimus is a substrate of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), encoded by the CYP3A and ATP-binding cassette subfamily B member 1 (ABCB1) genes, respectively. Tacrolimus 12-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 61-66 22310591-1 2012 BACKGROUND: Tacrolimus is a substrate of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), encoded by the CYP3A and ATP-binding cassette subfamily B member 1 (ABCB1) genes, respectively. Tacrolimus 12-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 110-115 22310591-2 2012 This study was aimed to investigate the impact of CYP3A and ABCB1 polymorphisms on the tacrolimus pharmacokinetics and clinical outcomes in Korean renal transplant recipients. Tacrolimus 87-97 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 50-55 22016125-8 2011 Calcineurin inhibitors (cyclosporine, tacrolimus) and mTOR inhibitors (sirolimus, everolimus) are particularly susceptible to the effects of substances that inhibit or induce cytochrome P450 (CYP) 3A4 and P-glycoprotein. Tacrolimus 38-48 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 175-200 21903774-0 2011 A new functional CYP3A4 intron 6 polymorphism significantly affects tacrolimus pharmacokinetics in kidney transplant recipients. Tacrolimus 68-78 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 17-23 21902502-1 2011 AIMS: CYP3A4 is involved in the oxidative metabolism of many drugs and xenobiotics including the immunosuppressants tacrolimus (Tac) and cyclosporine (CsA). Tacrolimus 116-126 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 6-12 21916909-0 2011 Association of ABCB1, CYP3A4*18B and CYP3A5*3 genotypes with the pharmacokinetics of tacrolimus in healthy Chinese subjects: a population pharmacokinetic analysis. Tacrolimus 85-95 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 22-28 21902502-1 2011 AIMS: CYP3A4 is involved in the oxidative metabolism of many drugs and xenobiotics including the immunosuppressants tacrolimus (Tac) and cyclosporine (CsA). Tacrolimus 128-131 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 6-12 21635144-0 2011 Impact of the CYP3A4*1G polymorphism and its combination with CYP3A5 genotypes on tacrolimus pharmacokinetics in renal transplant patients. Tacrolimus 82-92 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 14-20 21753749-0 2011 In vivo CYP3A activity is significantly lower in cyclosporine-treated as compared with tacrolimus-treated renal allograft recipients. Tacrolimus 87-97 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 8-13 21753749-1 2011 In vitro studies have identified cyclosporine and tacrolimus as CYP3A inhibitors. Tacrolimus 50-60 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 64-69 21753749-5 2011 This implies that in vivo hepatic and first-pass CYP3A activities are significantly lower in patients receiving cyclosporine than in those receiving tacrolimus, indicating that, at the doses generally used in clinical practice, cyclosporine is the stronger of the two with respect to CYP3A inhibition. Tacrolimus 149-159 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 49-54 21844990-13 2011 No significant clinical interaction or effect was observed, even with the use of atorvastatin or simvastatin, which are metabolized by CYP3A4 such as tacrolimus. Tacrolimus 150-160 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 135-141 21635144-1 2011 AIM: Tacrolimus is a substrate of CYP3A4 and CYP3A5. Tacrolimus 5-15 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 34-40 21635144-2 2011 The present study investigated the impact of the CYP3A4*1/*1G polymorphism compared with CYP3A5 genotypes on the dose-adjusted pharmacokinetics of tacrolimus. Tacrolimus 147-157 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 49-55 21635144-5 2011 RESULTS: The dose-adjusted AUC0-12 and C0 of tacrolimus were significantly lower in patients with the CYP3A4*1G allele and CYP3A5 expressers than those with the CYP3A4*1/*1 genotype and nonexpressers, respectively. Tacrolimus 45-55 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 102-108 21635144-5 2011 RESULTS: The dose-adjusted AUC0-12 and C0 of tacrolimus were significantly lower in patients with the CYP3A4*1G allele and CYP3A5 expressers than those with the CYP3A4*1/*1 genotype and nonexpressers, respectively. Tacrolimus 45-55 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 161-167 21635144-7 2011 The standardized regression coefficient for the AUC0-12 of tacrolimus was approximately twofold less for CYP3A4*1/*1 than CYP3A5*3/*3. Tacrolimus 59-69 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 105-111 21635144-9 2011 CONCLUSION: The CYP3A4*1/*1G polymorphism was associated with the pharmacokinetics of tacrolimus, however, its contribution to dose-adjusted pharmacokinetics was approximately twofold less than that of the CYP3A5*1/*3 polymorphism. Tacrolimus 86-96 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 16-22 21635144-10 2011 Although its effect on CYP3A4 activity is not clear, CYP3A4*1/*1G may be a candidate for a polymorphism affecting the interindividual variability in tacrolimus pharmacokinetics among CYP3A5 expressers. Tacrolimus 149-159 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 23-29 21635144-10 2011 Although its effect on CYP3A4 activity is not clear, CYP3A4*1/*1G may be a candidate for a polymorphism affecting the interindividual variability in tacrolimus pharmacokinetics among CYP3A5 expressers. Tacrolimus 149-159 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-59 20876828-8 2010 Tacrolimus, an immunosuppressant, is also a substrate of CYP3A and P-GP. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 57-62 21980965-2 2011 This was due to atazanavir and ritonavir therapy for her HIV inhibiting the CYP3A4 hepatic enzyme resulting in accumulation of tacrolimus. Tacrolimus 127-137 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 76-82 19667964-8 2009 Cyclosporine A and Tac are metabolized by CYP3A4 and CYP3A5, and several single nucleotide polymorphisms in the two genes have been associated with differences in drug clearance. Tacrolimus 19-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 42-48 21104927-7 2010 Simulations indicated that for a compound with greater metabolism by CYP3A5 than CYP3A4, such as tacrolimus, incorporation of the correlation between CYP3A4 and CYP3A5 does have an impact on the prediction of oral clearance. Tacrolimus 97-107 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 81-87 21104927-7 2010 Simulations indicated that for a compound with greater metabolism by CYP3A5 than CYP3A4, such as tacrolimus, incorporation of the correlation between CYP3A4 and CYP3A5 does have an impact on the prediction of oral clearance. Tacrolimus 97-107 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 150-156 21047202-4 2010 RESULTS: Four polymorphisms in CYP3A5 and one polymorphism in CYP3A4 were identified to be significantly associated with tacrolimus stable dose (p < 8.46 x 10(-5)). Tacrolimus 121-131 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 62-68 21047202-9 2010 Age, ethnicity and CYP3A inhibitor use could predict 30% of tacrolimus dosing variability. Tacrolimus 60-70 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 19-24 20832577-3 2010 Both tacrolimus and micafungin are substrates of cytochrome P450 3A4 in vitro. Tacrolimus 5-15 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 49-68 20718999-5 2010 Tibolone is known to be a weak competitive inhibitor of CYP3A4, which is involved in tacrolimus metabolism. Tacrolimus 85-95 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 56-62 20091056-5 2010 It also highlights the key role in tacrolimus pharmacokinetics of the CYP3A system and P-gp polymorphisms, and their influence in high-risk situations when enzyme activity is already affected by enterocyte damage due to diarrhoea and CCB competition. Tacrolimus 35-45 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 70-75 20097278-6 2010 Furthermore, 100 microM of WZ extract almost completely inhibited FK506 metabolism in rat and human liver microsomes, indicating WZ extract potently inhibited the CYP3A-mediated metabolism of FK506. Tacrolimus 192-197 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 163-168 20097278-7 2010 In conclusion, WZ inhibited P-gp-mediated efflux and CYP3A-mediated metabolism of FK506, and the reduction of intestinal first-pass effect by WZ was the major cause of the increased FK506 oral bioavailability. Tacrolimus 82-87 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-58 20305320-1 2010 BACKGROUND: Induction of the hepatic and intestinal cytochrome P450-3A4 system and intestinal P-glycoprotein is an unavoidable consequence of rifampin administration which requires substantial increase in tacrolimus dose when given concurrently. Tacrolimus 205-215 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 52-71 19813492-3 2009 Tacrolimus is metabolized by cytochrome P450 3A4 in both the liver and small intestine. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 29-48 19813492-4 2009 Drugs that are substrates of cytochrome P450 3A4, as well as inhibitors and inducers of cytochrome P450 3A4, can cause significant interactions with tacrolimus. Tacrolimus 149-159 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 29-48 19813492-4 2009 Drugs that are substrates of cytochrome P450 3A4, as well as inhibitors and inducers of cytochrome P450 3A4, can cause significant interactions with tacrolimus. Tacrolimus 149-159 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 88-107 19384171-2 2009 We have determined the genotypic frequencies of the CYP3A and ATP-binding cassette sub-family B member 1 (ABCB1) genes, which encode the CYP3A and P-gp proteins, respectively, in Korean organ transplant recipients and donors, and have assessed the influence of CYP3A and ABCB1 polymorphisms on tacrolimus concentrations. Tacrolimus 294-304 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 52-57 19384171-2 2009 We have determined the genotypic frequencies of the CYP3A and ATP-binding cassette sub-family B member 1 (ABCB1) genes, which encode the CYP3A and P-gp proteins, respectively, in Korean organ transplant recipients and donors, and have assessed the influence of CYP3A and ABCB1 polymorphisms on tacrolimus concentrations. Tacrolimus 294-304 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 137-142 19384171-2 2009 We have determined the genotypic frequencies of the CYP3A and ATP-binding cassette sub-family B member 1 (ABCB1) genes, which encode the CYP3A and P-gp proteins, respectively, in Korean organ transplant recipients and donors, and have assessed the influence of CYP3A and ABCB1 polymorphisms on tacrolimus concentrations. Tacrolimus 294-304 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 137-142 19289993-1 2009 BACKGROUND: Tacrolimus is a substrate of cytochrome P-450 (CYP) 3A enzyme and of the drug transporter ABCB1. Tacrolimus 12-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 41-66 19384171-0 2009 Tacrolimus concentrations in relation to CYP3A and ABCB1 polymorphisms among solid organ transplant recipients in Korea. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 41-46 19384171-1 2009 BACKGROUND: Cytochrome P450 3A (CYP3A) and the drug transporter P-glycoprotein (P-gp) affect the bioavailability of tacrolimus, the most commonly used immunosuppressive agent in organ transplant recipients. Tacrolimus 116-126 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 12-30 19384171-1 2009 BACKGROUND: Cytochrome P450 3A (CYP3A) and the drug transporter P-glycoprotein (P-gp) affect the bioavailability of tacrolimus, the most commonly used immunosuppressive agent in organ transplant recipients. Tacrolimus 116-126 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 32-37 19183931-7 2009 CYP3A4 inducers can lower levels of cyclosporine or tacrolimus so much that transplant rejection occurs, and CYP3A4 inhibitors can increase their levels, leading to nephrotoxicity. Tacrolimus 52-62 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 19376366-3 2009 The bioavailability of CsA and FK506 seems to be associated with the cytocrhome P450 IIIA (CYP3A) gene. Tacrolimus 31-36 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 91-96 19005401-1 2008 BACKGROUND: Bioavailability of tacrolimus (Tac) and cyclosporine is determined by cytochrome P450IIIA and by P-glycoprotein encoded by the CYP3A4/CYP3A5 and ABCB1 genes. Tacrolimus 31-41 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 139-145 19728747-9 2009 Ciclosporin and tacrolimus have distinct pharmacokinetics, but both are metabolized by intestinal and hepatic CYP3A4/3A5 and transported across the cell membrane by P-glycoprotein. Tacrolimus 16-26 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 110-116 18721002-3 2008 Cinacalcet, as well as some immunosuppressants such as ciclosporin, tacrolimus and sirolimus, is partially metabolized by the cytochrome P450 3A enzymes (CYP3A). Tacrolimus 68-78 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 154-159 18704002-2 2008 The aim of this study was to examine the influence of the CYP3A4, CYP3A5, and MDR1 single nucleotide polymorphisms on changes in tacrolimus exposure and dosing in renal allograft recipients treated with fluconazole. Tacrolimus 129-139 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 58-64 18556719-1 2008 Aprepitant (AP) is a known inhibitor of cytochrome P450 3A4 which may affect tacrolimus metabolism. Tacrolimus 77-87 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 40-59 18493655-4 2008 In support of this idea, we found that adding FKBP blocks binding of FK506 to the common cytochrome P(450) enzyme CYP3A4 in vitro. Tacrolimus 69-74 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 114-120 17979656-7 2007 The maximal F(G) ratios for the 11 CYP3A4 substrates investigated ranged from 1.06-7.14 for alprazolam and tacrolimus, respectively. Tacrolimus 107-117 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 35-41 17495880-5 2007 The lack of a time-related increase in dose-corrected tacrolimus exposure observed with the CYP3A4*1/CYP3A5*1 and CYP3A4*1B/CYP3A5*1 genotypes is associated with tacrolimus-related nephrotoxicity, possibly as a result of higher concentrations of toxic metabolites. Tacrolimus 54-64 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 92-98 17495880-5 2007 The lack of a time-related increase in dose-corrected tacrolimus exposure observed with the CYP3A4*1/CYP3A5*1 and CYP3A4*1B/CYP3A5*1 genotypes is associated with tacrolimus-related nephrotoxicity, possibly as a result of higher concentrations of toxic metabolites. Tacrolimus 54-64 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 114-120 17495880-5 2007 The lack of a time-related increase in dose-corrected tacrolimus exposure observed with the CYP3A4*1/CYP3A5*1 and CYP3A4*1B/CYP3A5*1 genotypes is associated with tacrolimus-related nephrotoxicity, possibly as a result of higher concentrations of toxic metabolites. Tacrolimus 162-172 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 114-120 18159131-2 2007 Since tacrolimus and PPIs share the CYP3A4 system for metabolism, pharmacokinetic interactions are anticipated when they are administered simultaneously. Tacrolimus 6-16 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 36-42 17495880-0 2007 CYP3A5 and CYP3A4 but not MDR1 single-nucleotide polymorphisms determine long-term tacrolimus disposition and drug-related nephrotoxicity in renal recipients. Tacrolimus 83-93 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 11-17 17495880-4 2007 The CYP3A4*1/CYP3A5*1 and CYP3A4*1B/CYP3A5*1 genotypes were significantly more frequently associated with the development of biopsy-proven tacrolimus-related nephrotoxicity than the CYP3A4*1/ CYP3A5*3 genotype (37.5 vs 11.2%; P=0.03 and 42.8 vs 11.2%; P=0.02). Tacrolimus 139-149 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 4-10 17495880-4 2007 The CYP3A4*1/CYP3A5*1 and CYP3A4*1B/CYP3A5*1 genotypes were significantly more frequently associated with the development of biopsy-proven tacrolimus-related nephrotoxicity than the CYP3A4*1/ CYP3A5*3 genotype (37.5 vs 11.2%; P=0.03 and 42.8 vs 11.2%; P=0.02). Tacrolimus 139-149 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 26-32 17495880-4 2007 The CYP3A4*1/CYP3A5*1 and CYP3A4*1B/CYP3A5*1 genotypes were significantly more frequently associated with the development of biopsy-proven tacrolimus-related nephrotoxicity than the CYP3A4*1/ CYP3A5*3 genotype (37.5 vs 11.2%; P=0.03 and 42.8 vs 11.2%; P=0.02). Tacrolimus 139-149 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 26-32 17889118-3 2007 The purpose of this study was to provide a short overview of recent results obtained in the field of pharmacogenetics of tacrolimus and sirolimus, both substrates of the cytochrome P450 3A (CYP3A) enzymes and of the efflux pump P-glycoprotein, the product of the Multidrug Resistance-1 (MDR1) genes. Tacrolimus 121-131 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 170-188 17889118-3 2007 The purpose of this study was to provide a short overview of recent results obtained in the field of pharmacogenetics of tacrolimus and sirolimus, both substrates of the cytochrome P450 3A (CYP3A) enzymes and of the efflux pump P-glycoprotein, the product of the Multidrug Resistance-1 (MDR1) genes. Tacrolimus 121-131 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 190-195 16424824-1 2006 It has been reported that hepatic and intestinal cytochrome P450 (CYP) 3A4, CYP3A5 and P-glycoprotein affect the pharmacokinetics of tacrolimus, and that these proteins are associated with the large inter-individual variation in the pharmacokinetics of this drug. Tacrolimus 133-143 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 49-74 17374625-8 2007 DATA SYNTHESIS: Elevated plasma concentrations and toxicities have been reported for a number of CYP3A substrates including amiodarone, carbamazepine, quinidine, tacrolimus, and cyclosporine when administered with metronidazole. Tacrolimus 162-172 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 97-102 16759707-5 2006 Both tacrolimus and cyclosporine are substrates of Pgp, CYP3A4 and CYP3A5, and therefore, these molecules are potential pharmacokinetic factors with which to establish personalized dosage regimens for these drugs. Tacrolimus 5-15 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 56-62 16906020-0 2006 Cyp3A4, Cyp3A5, and MDR-1 genetic influences on tacrolimus pharmacokinetics in renal transplant recipients. Tacrolimus 48-58 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 16906020-2 2006 Cytochrome P450 3A4 (Cyp3A4) and Cyp3A5 are the most important contributors to tacrolimus metabolism while the P-glycoprotein pump (MDR-1) modulates its bioavailability. Tacrolimus 79-89 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-19 16906020-2 2006 Cytochrome P450 3A4 (Cyp3A4) and Cyp3A5 are the most important contributors to tacrolimus metabolism while the P-glycoprotein pump (MDR-1) modulates its bioavailability. Tacrolimus 79-89 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 21-27 16906020-3 2006 The objective was to investigate the association between Cyp3A4, Cyp3A5, and MDR-1 polymorphisms and tacrolimus pharmacokinetics in the early period after renal transplantation. Tacrolimus 101-111 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 57-63 17202802-3 2007 On the other hand, cyclosporine and tacrolimus competitively inhibited CYP3A4-mediated nifedipine oxidation activity, with inhibition constants (K(i)) of 1.42 and 0.36 muM, respectively. Tacrolimus 36-46 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 71-77 16911928-6 2006 RESULTS: The SNPs of CYP3A and P-gp are closely correlated to the large variations of cyclosporine and tacrolimus dosage between different patients, although conflicting results were obtained by some authors. Tacrolimus 103-113 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 21-26 16753004-0 2006 Influence of different allelic variants of the CYP3A and ABCB1 genes on the tacrolimus pharmacokinetic profile of Chinese renal transplant recipients. Tacrolimus 76-86 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 47-52 16753004-2 2006 The cytochrome P450 3A (CYP3A) and the ATP-binding cassette B1 (ABCB1) genes play an important role in the tacrolimus disposition. Tacrolimus 107-117 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 4-22 16753004-2 2006 The cytochrome P450 3A (CYP3A) and the ATP-binding cassette B1 (ABCB1) genes play an important role in the tacrolimus disposition. Tacrolimus 107-117 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 24-29 16421475-2 2006 Tacrolimus is a substrate for CYP3A. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 30-35 16146556-2 2005 Cytochrome P450 (CYP) 3A and P-glycoprotein (P-gp, encoded by MDR1) play an important role in the absorption and metabolism of tacrolimus. Tacrolimus 127-137 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-24 15951320-11 2005 The importance of CYP3A5 status for tacrolimus clearance is also dependent on the concomitant CYP3A4 activity. Tacrolimus 36-46 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 94-100 16100295-1 2005 Tacrolimus is an approved immunosuppressive agent and a known substrate for CYP3A. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 76-81 15951320-1 2005 BACKGROUND: Tacrolimus is metabolized predominantly to 13-O-demethyltacrolimus in the liver and intestine by cytochrome P450 3A (CYP3A). Tacrolimus 12-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 109-127 15951320-1 2005 BACKGROUND: Tacrolimus is metabolized predominantly to 13-O-demethyltacrolimus in the liver and intestine by cytochrome P450 3A (CYP3A). Tacrolimus 12-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 129-134 15951320-2 2005 Patients with high concentrations of CYP3A5, a CYP3A isoenzyme polymorphically produced in these organs, require higher doses of tacrolimus, but the exact mechanism of this association is unknown. Tacrolimus 129-139 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 37-42 15919446-1 2005 The role of intestinal P-glycoprotein (encoded by the MDR1/ABCB1 gene) and/or metabolic enzyme CYP3A4 for tacrolimus therapy was examined in recipients of living-donor liver transplantation (LDLT), under the hypothesis that these proteins are factors for pharmacokinetic variability. Tacrolimus 106-116 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 95-101 15383495-2 2004 Tacrolimus absorption from the gastrointestinal tract is to a large extent determined by the genotypic, phenotypic, and functional expression of P-glycoprotein and CYP3A in the gut wall and liver. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 164-169 16038570-4 2005 Tacrolimus is primarily metabolised by cytochrome P450 (CYP) 3A enzymes in the gut wall and liver. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 39-63 16038570-6 2005 Age-associated alterations in CYP 3A and P-glycoprotein expression and/or activity, along with liver mass and body composition changes, would be expected to affect the pharmacokinetics of tacrolimus in the elderly. Tacrolimus 188-198 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 30-36 15698457-0 2005 Impact of gastric acid suppressants on cytochrome P450 3A4 and P-glycoprotein: consequences for FK506 assimilation. Tacrolimus 96-101 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 39-58 15698457-1 2005 BACKGROUND: Cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (PGP) are important determinants of the oral bioavailability and clearance of tacrolimus. Tacrolimus 138-148 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 12-31 15698457-1 2005 BACKGROUND: Cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (PGP) are important determinants of the oral bioavailability and clearance of tacrolimus. Tacrolimus 138-148 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 33-39 15197524-1 2004 OBJECTIVE: The aim of this study was to (a) quantify the gene expression of some cytochromes P(450) (CYP), especially CYP3A4, in serial biopsies from liver grafts the first year after orthoptic liver transplantation (OLT) and (b) study the relationship between hepatic CYP3A4 gene expression and plasma levels of cyclosporine and tacrolimus. Tacrolimus 330-340 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 118-124 15570183-9 2004 In vitro, MPA at concentrations above the plasma therapeutic range was found to decrease the metabolism of tacrolimus, suggesting a possible competition for CYP3A. Tacrolimus 107-117 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 157-162 15307840-0 2004 CYP3A4 and P-glycoprotein activity in healthy controls and transplant patients on cyclosporin vs. tacrolimus vs. sirolimus. Tacrolimus 98-108 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 15307840-1 2004 This study aimed to determine the impact of maintenance immunosuppressive therapy with cyclosporin A (CsA), tacrolimus (FK506) and sirolimus (Rapa) on the in vivo activity of both intestinal and hepatic cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (PGP) in renal transplant patients. Tacrolimus 120-125 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 203-222 15307840-1 2004 This study aimed to determine the impact of maintenance immunosuppressive therapy with cyclosporin A (CsA), tacrolimus (FK506) and sirolimus (Rapa) on the in vivo activity of both intestinal and hepatic cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (PGP) in renal transplant patients. Tacrolimus 120-125 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 224-230 15340245-1 2004 The oral bioavailability of tacrolimus is low and varies considerably in humans due to first-pass metabolism by cytochrome P450 (CYP) 3A4 and the active efflux mediated by P-glycoprotein. Tacrolimus 28-38 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 112-137 15518758-12 2004 Tacrolimus shows large variability in bioavailability after oral administration, both due to intestinal metabolism by cytochrome P450 (CYP3A4) and active secretion from enterocyte into intestinal lumen by P-glycoprotein. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 135-141 15197524-7 2004 The gene expression of CYP3A4 was related to the plasma concentration of cyclosporine and tacrolimus, i.e. low mRNA concentrations corresponded to high serum concentration levels and vice versa. Tacrolimus 90-100 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 23-29 15197524-11 2004 Low CYP3A4 gene expression was related to high plasma levels of cyclosporine and tacrolimus and vice versa. Tacrolimus 81-91 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 4-10 14632538-7 2003 DISCUSSION: Tacrolimus is metabolized in the liver via CYP3A4. Tacrolimus 12-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 55-61 15350151-5 2004 Drugs most prominently affected and contraindicated for concomitant use with St John"s wort are metabolised via both CYP3A4 and P-glycoprotein pathways, including HIV protease inhibitors, HIV non-nucleoside reverse transcriptase inhibitors (only CYP3A4), the immunosuppressants ciclosporin and tacrolimus, and the antineoplastic agents irinotecan and imatinib mesylate. Tacrolimus 294-304 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 117-123 15010519-9 2004 Since tacrolimus is also metabolized by CYP3A4, the blood concentration of tacrolimus in this patient who had a CYP2C19 gene mutation may have been elevated by decreased hepatic elimination of lansoprazole. Tacrolimus 6-16 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 40-46 15010519-9 2004 Since tacrolimus is also metabolized by CYP3A4, the blood concentration of tacrolimus in this patient who had a CYP2C19 gene mutation may have been elevated by decreased hepatic elimination of lansoprazole. Tacrolimus 75-85 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 40-46 14870897-1 2003 Azole antifungals inhibit the metabolism of tacrolimus mediated by CYP3A4. Tacrolimus 44-54 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 67-73 14578760-2 2003 Tacrolimus is a substrate of cytochrome p450 (CYP), of subfamily CYP3A. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 65-70 14551375-1 2003 BACKGROUND: Tacrolimus is an immunosuppressive drug that is a substrate of cytochrome P450 3A (CYP3A) enzymes and P-glycoprotein (P-gp). Tacrolimus 12-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 75-93 14551375-1 2003 BACKGROUND: Tacrolimus is an immunosuppressive drug that is a substrate of cytochrome P450 3A (CYP3A) enzymes and P-glycoprotein (P-gp). Tacrolimus 12-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 95-100 12966368-0 2003 Genetic polymorphisms of the CYP3A4, CYP3A5, and MDR-1 genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus. Tacrolimus 129-139 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 29-35 12966368-10 2003 CONCLUSION: As a group, patients with the CYP3A5*3/*3 genotype require less tacrolimus to reach target predose concentrations compared with CYP3A5*1 allele carriers, whereas CYP3A4*1B carriers require more tacrolimus to reach target trough concentrations compared with CYP3A4*1 homozygotes. Tacrolimus 206-216 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 174-180 12966368-3 2003 OBJECTIVE: Our objective was to determine the role of genetic polymorphisms in CYP3A4, CYP3A5, and MDR-1 with respect to interindividual variability in cyclosporine and tacrolimus pharmacokinetics. Tacrolimus 169-179 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 79-85 12966368-7 2003 CYP3A4*1B allele carriers (n = 10) had lower tacrolimus dose-adjusted trough levels compared with those in patients with the wild-type (*1/*1) genotype (n = 54): median and range, 57 (40-163) ng/mL per mg/kg versus 89 (34-398) ng/mL per mg/kg) (P =.003, Mann-Whitney test). Tacrolimus 45-55 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 12966368-10 2003 CONCLUSION: As a group, patients with the CYP3A5*3/*3 genotype require less tacrolimus to reach target predose concentrations compared with CYP3A5*1 allele carriers, whereas CYP3A4*1B carriers require more tacrolimus to reach target trough concentrations compared with CYP3A4*1 homozygotes. Tacrolimus 76-86 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 269-275 12685503-1 2002 Tacrolimus, a potent immunosuppressive drug, is known to be metabolized predominantly in the liver by cytochrome P450 3A (CYP3A). Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 102-120 12826147-2 2003 Ketoconazole increases tacrolimus bioavailability by inhibiting cytochrome P450 3A4 and glycoprotein-p. Tacrolimus 23-33 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 64-83 12694072-2 2003 P-gp is encoded by the multiple drug resistance gene MDR1 and CYP3A is the major enzyme responsible for tacrolimus metabolism. Tacrolimus 104-114 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 62-67 12685503-1 2002 Tacrolimus, a potent immunosuppressive drug, is known to be metabolized predominantly in the liver by cytochrome P450 3A (CYP3A). Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 122-127 12685503-5 2002 Tacrolimus had no effect on any CYP at concentrations below 1 microM, while at higher concentrations it had a mild inhibitory effect on CYP3A4 and 3A5. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 136-142 12451243-0 2002 Lowered blood concentration of tacrolimus and its recovery with changes in expression of CYP3A and P-glycoprotein after high-dose steroid therapy. Tacrolimus 31-41 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 89-94 12451243-10 2002 CONCLUSION: Our results indicate that the decrease in the blood FK506 concentration caused by high-dose steroid therapy is a consequence of the induction of P-glycoprotein and CYP3A in the liver and intestine, and these changes were reversed within 2 weeks after cessation of steroid therapy. Tacrolimus 64-69 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 176-181 12190331-11 2002 In the near future, progress can be expected from studies evaluating potential pharmacokinetic interactions caused by herbal preparations and food components, the exact biochemical mechanism underlying tacrolimus toxicity, and the potential of inhibition of CYP3A and P-glycoprotein to improve oral bioavailability and to decrease intraindividual variability of tacrolimus pharmacokinetics. Tacrolimus 362-372 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 258-263 11923712-0 2002 Tacrolimus-induced nephrotoxicity unmasked by induction of the CYP3A4 system with St John"s wort. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 63-69 11397967-1 2001 BACKGROUND: Tacrolimus, a substrate of CYP3A, has low and variable bioavailability similar to cyclosporine. Tacrolimus 12-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 39-44 12190331-2 2002 As a substrate of cytochrome P450 (CYP) 3A enzymes and P-glycoprotein, tacrolimus interacts with several other drugs used in transplantation medicine, which also are known CYP3A and/or P-glycoprotein inhibitors and/or inducers. Tacrolimus 71-81 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 18-42 12190331-2 2002 As a substrate of cytochrome P450 (CYP) 3A enzymes and P-glycoprotein, tacrolimus interacts with several other drugs used in transplantation medicine, which also are known CYP3A and/or P-glycoprotein inhibitors and/or inducers. Tacrolimus 71-81 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 172-177 12190331-3 2002 In clinical studies, CYP3A/P-glycoprotein inhibitors and inducers primarily affect oral bioavailability of tacrolimus rather than its clearance, indicating a key role of intestinal P-glycoprotein and CYP3A. Tacrolimus 107-117 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 21-26 12190331-3 2002 In clinical studies, CYP3A/P-glycoprotein inhibitors and inducers primarily affect oral bioavailability of tacrolimus rather than its clearance, indicating a key role of intestinal P-glycoprotein and CYP3A. Tacrolimus 107-117 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 200-205 11719731-1 2001 BACKGROUND: Interindividual variation in the pharmacokinetics of the immunosuppressive agents cyclosporine (INN, ciclosporin) and tacrolimus may result from differences in the activity of cytochrome P4503A (CYP3A). Tacrolimus 130-140 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 188-194 11719731-1 2001 BACKGROUND: Interindividual variation in the pharmacokinetics of the immunosuppressive agents cyclosporine (INN, ciclosporin) and tacrolimus may result from differences in the activity of cytochrome P4503A (CYP3A). Tacrolimus 130-140 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 207-212 12167066-4 2002 Oral bioavailability of tacrolimus can be increased by concomitant administration of inhibitors of either CYP3A or P-glycoprotein. Tacrolimus 24-34 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 106-111 12497749-1 2002 AIM: Hepatic metabolism of sildenafil uses the same metabolic pathway as the calcineurin inhibitors (cyclosporine/tacrolimus), through the CYP3A4 isoenzyme. Tacrolimus 114-124 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 139-145 11397967-2 2001 Co-administration of ketoconazole, potent inhibitor of gut and hepatic CYP3A, has been shown to increase tacrolimus bioavailability in healthy volunteers. Tacrolimus 105-115 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 71-76 11239516-1 2001 OBJECTIVES: Little is known about the effect of ischemia/reperfusion with xenogenic blood on function and gene expression of CYP3A4, the enzyme largely responsible for the metabolism of the immunosuppressants Cyclosporin A (CsA) and Tacrolimus. Tacrolimus 233-243 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 125-131 9987705-7 1999 Rifampin appears to induce both intestinal and hepatic metabolism of tacrolimus, most likely through induction of CYP3A and P-glycoprotein in the liver and small bowel. Tacrolimus 69-79 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 114-119 10731062-3 2000 As CYP3A4 enzymes and P-gp are present at differing concentrations throughout the gastrointestinal tract, the bioavailability of tacrolimus may be influenced by changes in gastrointestinal transit time in addition to changes in hepatic metabolism. Tacrolimus 129-139 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 3-9 10440408-5 1999 We hypothesize that the protease inhibitors" competition for binding to cytochrome P450 isoenzyme system CYP3A induced extreme prolongation of tacrolimus metabolism. Tacrolimus 143-153 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 105-110 10410178-9 1999 DISCUSSION: Tacrolimus is known to be a substrate for P-glycoprotein and metabolized by CYP3A. Tacrolimus 12-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 88-93 10837558-14 1997 It seems that compounds that alter (either induce or inhibit) CYP3A4 and/or p-glycoprotein will alter the oral pharmacokinetics of cyclosporine and tacrolimus. Tacrolimus 148-158 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 62-68 9808496-1 1998 BACKGROUND: Although it is important to maintain an appropriate blood concentration of FK506 after liver transplantation, significant interindividual variability in the actual FK506 dosage has been observed, presumably due to the wide variability of cytochrome P450 3A4 activity in liver microsomes. Tacrolimus 176-181 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 250-269 9808502-1 1998 BACKGROUND/AIMS: Tacrolimus is metabolized by cytochrome P450 3A4 and 2D6 and has a narrow therapeutic range. Tacrolimus 17-27 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 46-73 9246018-1 1997 OBJECTIVE: To quantitate the effect of ketoconazole, an azole antifungal agent and potent inhibitor of CYP3A4 and P-glycoprotein, on the bioavailability of tacrolimus, a substrate of the CYP3A system and of P-glycoprotein. Tacrolimus 156-166 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 103-108 10837558-2 1997 Cyclosporine and tacrolimus are metabolized primarily by cytochrome P450 3A4 (CYP3A4) in the liver and small intestine. Tacrolimus 17-27 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 57-76 10837558-2 1997 Cyclosporine and tacrolimus are metabolized primarily by cytochrome P450 3A4 (CYP3A4) in the liver and small intestine. Tacrolimus 17-27 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 78-84 8689938-9 1995 The metabolism of tacrolimus by human small intestine was inhibited by anti-CYP3A, troleandomycin, and erythromycin, indicating that, as in the liver, CYP3A enzymes are the major enzymes for tacrolimus metabolism in the human small intestine. Tacrolimus 18-28 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 76-81 8857552-2 1996 Interpatient differences in liver CYP3A4 activity, as measured by the ERMBT, seem to account, for the most part, for interindividual differences in the kinetics of cyclosporin A and FK506. Tacrolimus 182-187 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 34-40 8689938-9 1995 The metabolism of tacrolimus by human small intestine was inhibited by anti-CYP3A, troleandomycin, and erythromycin, indicating that, as in the liver, CYP3A enzymes are the major enzymes for tacrolimus metabolism in the human small intestine. Tacrolimus 18-28 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 151-156 8689938-9 1995 The metabolism of tacrolimus by human small intestine was inhibited by anti-CYP3A, troleandomycin, and erythromycin, indicating that, as in the liver, CYP3A enzymes are the major enzymes for tacrolimus metabolism in the human small intestine. Tacrolimus 191-201 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 76-81 8689938-9 1995 The metabolism of tacrolimus by human small intestine was inhibited by anti-CYP3A, troleandomycin, and erythromycin, indicating that, as in the liver, CYP3A enzymes are the major enzymes for tacrolimus metabolism in the human small intestine. Tacrolimus 191-201 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 151-156 8689938-13 1995 It is concluded that tacrolimus is metabolized by cytochrome CYP3A enzymes in the small intestine. Tacrolimus 21-31 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 61-66 8689938-14 1995 The rate of the CYP3A enzymatic activities varies about 5 times from patient to patient, and drugs that interfere with the in vitro metabolism of tacrolimus in the liver also inhibit its small intestinal metabolism. Tacrolimus 146-156 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 16-21 7552894-4 1995 Tacrolimus is extensively metabolized by cytochrome P-450 3A4 isoenzyme, resulting in several known drug interactions. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 41-61 19709321-8 2009 Increased tacrolimus half-life and increased dose interval of sirolimus and tacrolimus were due to CYP3A4/5 and/or P-glycoprotein inhibition by protease inhibitors. Tacrolimus 10-20 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 99-105 7628296-9 1995 Therefore, compounds interacting with CYP3A proteins are expected to cause drug-drug interactions (i.e. the antimycotics ketoconazole and clotrimazole, the steroids ethinylestradiol and testosterone, the ergots, the calcium channel blocker nifedipine, and the immunosuppressants FK-506 and rapamycin). Tacrolimus 279-285 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 38-43 19709321-8 2009 Increased tacrolimus half-life and increased dose interval of sirolimus and tacrolimus were due to CYP3A4/5 and/or P-glycoprotein inhibition by protease inhibitors. Tacrolimus 76-86 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 99-105 34781138-0 2022 Trans-eQTLs of the CYP3A4 and CYP3A5 associated with tacrolimus trough blood concentration in Chinese renal transplant patients. Tacrolimus 53-63 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 19-25 34688813-1 2022 AIM: The purpose of this study was to investigate the effect of CYP3A7, CYP3A4, and CYP3A5 genetic polymorphisms in liver transplant recipients and donors on tacrolimus concentrations in the early stages after liver transplantation. Tacrolimus 158-168 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 72-78 34688813-4 2022 RESULTS: Recipient CYP3A polymorphisms were associated with tacrolimus concentrations. Tacrolimus 60-70 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 19-24 34688813-7 2022 Regardless of the genotype of the matched donor, CYP3A7 rs10211, CYP3A4*1G (rs2242480), and CYP3A5*3 (rs776746) polymorphisms of recipients could affect tacrolimus concentrations. Tacrolimus 153-163 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 65-71 34688813-8 2022 For the CYP3A4 rs4646437 polymorphisms, when the donor carried CYP3A4 rs4646437 CC, the recipient CYP3A4 rs4646437 polymorphism was associated with the C0/D of tacrolimus, and when the donor carried CYP3A4 rs4646437 CT/TT genotype, the recipient CYP3A4 rs4646437 polymorphism also affected on tacrolimus C0/D, although the effect was not significant. Tacrolimus 160-170 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 98-104 34688813-8 2022 For the CYP3A4 rs4646437 polymorphisms, when the donor carried CYP3A4 rs4646437 CC, the recipient CYP3A4 rs4646437 polymorphism was associated with the C0/D of tacrolimus, and when the donor carried CYP3A4 rs4646437 CT/TT genotype, the recipient CYP3A4 rs4646437 polymorphism also affected on tacrolimus C0/D, although the effect was not significant. Tacrolimus 293-303 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 246-252 34688813-9 2022 CONCLUSION: The large inter-individual variation in tacrolimus concentrations in the early stages after liver transplantation is influenced by genetic polymorphisms of CYP3A7, CYP3A4, and CYP3A5. Tacrolimus 52-62 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 176-182 34688813-11 2022 Therefore, the detection of CYP3A polymorphisms in recipients could help to predict the tacrolimus starting dose in the early stages after liver transplantation. Tacrolimus 88-98 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 28-33 34781138-1 2022 This study aimed to systematically investigate trans-eQTLs of CYP3A4 and CYP3A5 affecting tacrolimus trough blood concentrations in Chinese renal transplant patients. Tacrolimus 90-100 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 62-68 34725418-4 2021 In low CYP3A4 expressers carrying CYP3A5*3/*3, the dose-corrected tacrolimus level was significantly higher than in normal CYP3A4 expressers or in those with CYP3A5*1. Tacrolimus 66-76 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 7-13 34583027-1 2022 BACKGROUND: CYP3A5 and CYP3A4 are the predominant enzymes responsible for tacrolimus metabolism, however only a proportion of the population expresses CYP3A5 secondary to genetic variation. Tacrolimus 74-84 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 23-29 34583027-12 2022 RESULTS: CYP3A5 and CYP3A4 genotypes were significantly associated with the IV C/D with CYP3A5 expressers having 20% lower and CYP3A4 rapid metabolizers having 20% lower tacrolimus exposure. Tacrolimus 170-180 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 20-26 34583027-12 2022 RESULTS: CYP3A5 and CYP3A4 genotypes were significantly associated with the IV C/D with CYP3A5 expressers having 20% lower and CYP3A4 rapid metabolizers having 20% lower tacrolimus exposure. Tacrolimus 170-180 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 127-133 34725418-0 2021 CYP3A-status is associated with blood concentration and dose-requirement of tacrolimus in heart transplant recipients. Tacrolimus 76-86 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-5 34725418-5 2021 Modification of the initial tacrolimus dose was required for all patients: dose reduction by 20% for low CYP3A4 expressers, a 40% increase for normal expressers and a 2.4-fold increase for CYP3A5*1 carriers. Tacrolimus 28-38 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 105-111 34725418-1 2021 High inter-individual variability in tacrolimus clearance is attributed to genetic polymorphisms of CYP3A enzymes. Tacrolimus 37-47 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 100-105 34725418-8 2021 Although monitoring of tacrolimus blood concentration cannot be omitted, assaying recipients" CYP3A-status can guide optimization of the initial tacrolimus dose, and can facilitate personalized tacrolimus therapy during steroid withdrawal in the late post-operative period. Tacrolimus 145-155 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 94-99 34725418-2 2021 However, due to CYP3A phenoconversion induced by non-genetic factors, continuous changes in tacrolimus-metabolizing capacity entail frequent dose-refinement for optimal immunosuppression. Tacrolimus 92-102 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 16-21 34285488-2 2021 Wuzhi capsule (WZC) could improve tacrolimus blood concentration by inhibiting the metabolism of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp). Tacrolimus 34-44 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 97-115 34285488-2 2021 Wuzhi capsule (WZC) could improve tacrolimus blood concentration by inhibiting the metabolism of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp). Tacrolimus 34-44 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 117-122 34306041-9 2021 CYP3A4*22 was shown to significantly influence the pharmacokinetics of several drugs, with currently being most thoroughly investigated tacrolimus, cyclosporine, and statins. Tacrolimus 136-146 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 34130909-2 2022 Each of the compounds are substrates of CYP3A4/5, the cytochrome P450 enzyme family for which tacrolimus is also a substrate. Tacrolimus 94-104 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 40-48 35562875-0 2022 Examination of the Impact of CYP3A4/5 on Drug-Drug Interaction between Schizandrol A/Schizandrol B and Tacrolimus (FK-506): A Physiologically Based Pharmacokinetic Modeling Approach. Tacrolimus 103-113 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 29-37 35562875-0 2022 Examination of the Impact of CYP3A4/5 on Drug-Drug Interaction between Schizandrol A/Schizandrol B and Tacrolimus (FK-506): A Physiologically Based Pharmacokinetic Modeling Approach. Tacrolimus 115-121 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 29-37 35562875-2 2022 Due to their inhibitory effects on cytochrome P450 (CYP) 3A enzymes, SZA/SZB may display drug-drug interaction (DDI) with tacrolimus. Tacrolimus 122-132 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 35-59 34620272-3 2021 Cytochrome-P450 (CYP) isoenzymes CYP3A4 and CYP3A5, as well P-glycoprotein (P-gp) are involved in TAC bioavailability. Tacrolimus 98-101 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 33-39 35389944-0 2022 Composite CYP3A phenotypes influence tacrolimus dose-adjusted concentration in lung transplant recipients. Tacrolimus 37-47 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 10-15 35389944-1 2022 OBJECTIVES: Interpatient variability in tacrolimus pharmacokinetics is attributed to metabolism by cytochrome P-450 3A4/5 isoenzymes (encoded by CYP3A4 and CYP3A5). Tacrolimus 40-50 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 99-121 35389944-1 2022 OBJECTIVES: Interpatient variability in tacrolimus pharmacokinetics is attributed to metabolism by cytochrome P-450 3A4/5 isoenzymes (encoded by CYP3A4 and CYP3A5). Tacrolimus 40-50 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 145-151 35389944-2 2022 Guidelines for adjusting tacrolimus based on CYP3A5 test results are published; however, CYP3A4 variants also contribute to the variability in tacrolimus pharmacokinetics. Tacrolimus 143-153 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 89-95 35389944-4 2022 The objective of this study is to investigate the impact of both increased and decreased function CYP3A variants on weight and dose-adjusted tacrolimus concentration (C0/D). Tacrolimus 141-151 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 98-103 35389944-13 2022 CONCLUSION: These data indicate that a composite CYP3A phenotype incorporating both increase and decrease variant information from CYP3A4 in addition to CYP3A5 may significantly influence tacrolimus C0/D during the early postoperative period. Tacrolimus 188-198 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 49-54 35389944-13 2022 CONCLUSION: These data indicate that a composite CYP3A phenotype incorporating both increase and decrease variant information from CYP3A4 in addition to CYP3A5 may significantly influence tacrolimus C0/D during the early postoperative period. Tacrolimus 188-198 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 131-137 35396676-0 2022 Interactions with the CYP3A inhibitor voriconazole differ between extended-LCP- and immediate-release tacrolimus formulations. Tacrolimus 102-112 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 22-27 35599203-4 2022 Tacrolimus is metabolized by the cytochrome P450 3A4 enzyme system. Tacrolimus 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 33-52