PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 9618413-4 1998 Anti-CYP3A antibodies, as well as the specific CYP3A inhibitors troleandomycin and erythromycin, inhibited small intestinal metabolism of sirolimus, confirming that, as in the liver, CYP3A enzymes are responsible for sirolimus metabolism in the small intestine. Sirolimus 138-147 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 5-10 9618413-4 1998 Anti-CYP3A antibodies, as well as the specific CYP3A inhibitors troleandomycin and erythromycin, inhibited small intestinal metabolism of sirolimus, confirming that, as in the liver, CYP3A enzymes are responsible for sirolimus metabolism in the small intestine. Sirolimus 138-147 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 47-52 9618413-4 1998 Anti-CYP3A antibodies, as well as the specific CYP3A inhibitors troleandomycin and erythromycin, inhibited small intestinal metabolism of sirolimus, confirming that, as in the liver, CYP3A enzymes are responsible for sirolimus metabolism in the small intestine. Sirolimus 138-147 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 47-52 9618413-4 1998 Anti-CYP3A antibodies, as well as the specific CYP3A inhibitors troleandomycin and erythromycin, inhibited small intestinal metabolism of sirolimus, confirming that, as in the liver, CYP3A enzymes are responsible for sirolimus metabolism in the small intestine. Sirolimus 217-226 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 5-10 9618413-5 1998 Of 32 drugs tested, only known CYP3A substrates inhibited sirolimus intestinal metabolism with inhibitor constants (Ki) equal to those in human liver microsomes. Sirolimus 58-67 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 31-36 9618413-8 1998 Intestinal drug metabolism and countertransport into the gut lumen, drug interactions with CYP3A substrates and inhibitors in the small intestine and an 8-fold interindividual variability of the intestinal metabolite formation rate significantly contribute to the low and highly variable bioavailability of sirolimus. Sirolimus 307-316 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 91-96 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. Sirolimus 62-71 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). Sirolimus 290-299 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 38-43 30295407-1 2019 INTRODUCTION: Isavuconazole, a triazole antifungal, is an inhibitor of cytochrome P450 3A4, which also metabolizes tacrolimus and sirolimus. Sirolimus 130-139 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 71-90 33991364-4 2021 Previous reports indicate increased systemic exposures of cyclosporine and sirolimus in patients receiving high-dose marine omega-3 FA supplements (3, 4) which could be related to reduced drug metabolism supported by the in vitro experimental observation of an inhibitory effect of omega-3 FAs on cytochrome P450 (CYP) 3A enzymes (5) expressed in the intestine and liver. Sirolimus 75-84 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 297-321 33115392-0 2020 The genetic polymorphism of CYP3A4 rs2242480 is associated with sirolimus trough concentrations among adult renal transplant recipients. Sirolimus 64-73 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 28-34 29668485-3 2018 Pharmacokinetic assays of sirolimus are available as this drug has a precise therapeutic window and blood levels might be influenced by CYP3A4 polymorphisms and drug interactions. Sirolimus 26-35 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 136-142 28676933-2 2017 The metabolism of temsirolimus and its active metabolite sirolimus mainly depends on cytochrome P450 3A4/5 (CYP3A4/A5) and the ABCB1 transporter. Sirolimus 21-30 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 85-106 28355970-2 2018 Sirolimus is metabolized by cytochrome P450 3A4 and is a substrate of the P-glycoprotein (P-gp) drug efflux pump. Sirolimus 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 28-47 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. Sirolimus 160-169 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 38-57 28676933-2 2017 The metabolism of temsirolimus and its active metabolite sirolimus mainly depends on cytochrome P450 3A4/5 (CYP3A4/A5) and the ABCB1 transporter. Sirolimus 21-30 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 108-114 27530708-1 2016 Being a substrate of the cytochrome P450 3A4 (CYP3A4) isoenzyme, sirolimus metabolism is decreased when posaconazole is administered concomitantly. Sirolimus 65-74 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 25-44 28700521-0 2017 Effect of CYP3A4 and CYP3A5 Genetic Polymorphisms on the Pharmacokinetics of Sirolimus in Healthy Chinese Volunteers. Sirolimus 77-86 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 10-16 28700521-3 2017 Sirolimus is primarily metabolized by cytochrome CYP3A4 and CYP3A5. Sirolimus 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 49-55 28700521-4 2017 This study aimed to clarify the effect of CYP3A genetic polymorphisms, including the CYP3A4*1G and CYP3A5*3 polymorphisms, on the pharmacokinetics of sirolimus. Sirolimus 150-159 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 42-47 28700521-4 2017 This study aimed to clarify the effect of CYP3A genetic polymorphisms, including the CYP3A4*1G and CYP3A5*3 polymorphisms, on the pharmacokinetics of sirolimus. Sirolimus 150-159 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 85-91 28700521-12 2017 CONCLUSIONS: CYP3A4 and CYP3A5 genetic polymorphisms are important factors affecting pharmacokinetic parameters of sirolimus. Sirolimus 115-124 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 13-19 28700521-13 2017 Our data support the monitoring of blood sirolimus concentrations, especially in CYP3A5*1 and CYP3A4*1 G carriers, to ensure accurate dosing in the clinical setting. Sirolimus 41-50 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 94-100 27530708-1 2016 Being a substrate of the cytochrome P450 3A4 (CYP3A4) isoenzyme, sirolimus metabolism is decreased when posaconazole is administered concomitantly. Sirolimus 65-74 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 46-52 25599164-2 2015 Although sirolimus is being used increasingly for the prevention of GVHD, it is a substrate of CYP3A4, which is inhibited by voriconazole, and concurrent administration can lead to significantly increased exposure to sirolimus. Sirolimus 9-18 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 95-101 27501453-6 2016 CYP3A-dependent sirolimus metabolite formation changed in a similar fashion. Sirolimus 16-25 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-5 26256674-1 2015 AIMS: Sirolimus is an mTOR inhibitor metabolized by CYP3A4 and CYP3A5. Sirolimus 6-15 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 52-58 26256674-9 2015 The PBPK model developed based on CL(int) of recombinant CYP3A4, CYP3A5 and CYP2C8 predicted a small CYP3A5*3 effect on simulated sirolimus PK profiles. Sirolimus 130-139 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 57-63 26232156-9 2015 In the first case, the cause was revealed to be a drug that was added to the patient"s treatment regimen (posaconazole) that inhibits CYP3A4 which is responsible for sirolimus metabolism. Sirolimus 166-175 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 134-140 26151793-7 2015 It is postulated that this interaction was mediated by acitretin inhibition of CYP3A4, the primary enzyme responsible for sirolimus metabolism. Sirolimus 122-131 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 79-85 25162215-10 2015 CONCLUSIONS: This study suggests that the age-dependent changes in sirolimus clearance can be explained by size-related increases in CYP3A metabolic capacity, most likely due to liver and intestinal growth. Sirolimus 67-76 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 133-138 25599164-2 2015 Although sirolimus is being used increasingly for the prevention of GVHD, it is a substrate of CYP3A4, which is inhibited by voriconazole, and concurrent administration can lead to significantly increased exposure to sirolimus. Sirolimus 217-226 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 95-101 26225230-5 2015 Simulated clearance estimates with a sirolimus physiologically based pharmacokinetic model that included CYP3A4/5/7 and CYP2C8 maturation profiles were in close agreement with observed in vivo clearance values. Sirolimus 37-46 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 105-111 27128230-1 2014 Sirolimus, metabolized primarily by intestinal and hepatic CYP3A4, is a substrate for P-glycoprotein. Sirolimus 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 59-65 24575309-9 2014 Since ranolazine is a documented P-GP and CYP3A inhibitor, and sirolimus a known substrate for both pathways, it is proposed that ranolazine inhibition of P-GP and CYP3A4 contributed to the significant elevation in sirolimus exposure. Sirolimus 215-224 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 164-170 27128230-2 2014 CYP3A4 inducers would be expected to decrease sirolimus exposure. Sirolimus 46-55 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 27128230-3 2014 This open-label, nonrandomized study investigated effects of CYP3A4 induction, by rifampin, on sirolimus pharmacokinetics. Sirolimus 95-104 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 61-67 18458675-3 2008 Because temsirolimus and its primary metabolite, sirolimus, are metabolised by the cytochrome P450 3A4 pathway (CYP3A4), the potential exists for pharmacokinetic (PK) drug interactions with the numerous agents that modulate CYP3A4 isozyme activity. Sirolimus 11-20 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 83-102 23974086-8 2013 RESULTS: In vitro, the CYP3A4*22 allele resulted in approximately 20% lower metabolic rates of SRL (P = 0.0411). Sirolimus 95-98 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 23-29 23884207-0 2013 Development of a Physiologically-Based Pharmacokinetic Model for Sirolimus: Predicting Bioavailability Based on Intestinal CYP3A Content. Sirolimus 65-74 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 123-128 22564264-3 2012 As posaconazole strongly inhibits CYP3A4, concurrent administration of sirolimus, a CYP3A4 substrate, and posaconazole has been reported to increase sirolimus drug exposure substantially. Sirolimus 71-80 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 34-40 22564264-3 2012 As posaconazole strongly inhibits CYP3A4, concurrent administration of sirolimus, a CYP3A4 substrate, and posaconazole has been reported to increase sirolimus drug exposure substantially. Sirolimus 71-80 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 84-90 22564264-3 2012 As posaconazole strongly inhibits CYP3A4, concurrent administration of sirolimus, a CYP3A4 substrate, and posaconazole has been reported to increase sirolimus drug exposure substantially. Sirolimus 149-158 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 34-40 22564264-3 2012 As posaconazole strongly inhibits CYP3A4, concurrent administration of sirolimus, a CYP3A4 substrate, and posaconazole has been reported to increase sirolimus drug exposure substantially. Sirolimus 149-158 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 84-90 22094953-1 2011 BACKGROUNDS: Sirolimus (SRL) absorption and metabolism are affected by p-glycoprotein-mediated transport and CYP3A enzyme activity, which are further under the influences of cytokine concentrations. Sirolimus 13-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 109-114 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. Sirolimus 71-80 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 175-200 19728747-14 2009 Proliferation signal inhibitors (PSIs) such as sirolimus and everolimus are substrates of CYP3A4 and P-glycoprotein and have a macrolide structure very similar to tacrolimus, which explains why common drug interactions with PSIs are comparable to those with calcineurin inhibitors. Sirolimus 47-56 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 90-96 18458675-3 2008 Because temsirolimus and its primary metabolite, sirolimus, are metabolised by the cytochrome P450 3A4 pathway (CYP3A4), the potential exists for pharmacokinetic (PK) drug interactions with the numerous agents that modulate CYP3A4 isozyme activity. Sirolimus 11-20 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 112-118 18458675-3 2008 Because temsirolimus and its primary metabolite, sirolimus, are metabolised by the cytochrome P450 3A4 pathway (CYP3A4), the potential exists for pharmacokinetic (PK) drug interactions with the numerous agents that modulate CYP3A4 isozyme activity. Sirolimus 11-20 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 224-230 17913896-2 2007 Because temsirolimus and its metabolite, sirolimus, are cytochrome P450 (CYP) 3A4/5 substrates, the potential exists for interaction with drugs that induce CYP3A activity, including enzyme inducers and rifampin. Sirolimus 11-20 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 156-161 18094423-13 2007 CONCLUSIONS: Drugs that induce cytochrome P450 3A4, such as EIAEDs, significantly affect the pharmacokinetics of temsirolimus and its active metabolite, sirolimus. Sirolimus 116-125 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 31-50 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). Sirolimus 83-92 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 154-159 15686733-1 2004 Sirolimus, a new immunosuppressant drug; is metabolized by cytochrome P450 3A4 (CYP3A4) and is a substrate of the P-glycoprotein drug efflux pump. Sirolimus 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 59-78 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. Sirolimus 136-145 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. Sirolimus 136-145 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 190-195 15686733-1 2004 Sirolimus, a new immunosuppressant drug; is metabolized by cytochrome P450 3A4 (CYP3A4) and is a substrate of the P-glycoprotein drug efflux pump. Sirolimus 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 80-86 11907172-10 2002 Along with CYP3A4-mediated metabolism and P-gp-mediated secretion, we conclude that the following novel pathway, which occurs at least in the intestine, may contribute significantly to the first-pass extraction of sirolimus in humans: intracellular degradation of sirolimus to seco-rapamycin, metabolism of seco-rapamycin to M2 by an unidentified non-microsomal enzyme, and P-gp-mediated secretion of M2 and seco-rapamycin. Sirolimus 264-273 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 11-17 15760093-8 2004 Sirolimus is a substrate for both Cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp) and undergoes extensive first-pass extraction. Sirolimus 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 34-52 15760093-8 2004 Sirolimus is a substrate for both Cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp) and undergoes extensive first-pass extraction. Sirolimus 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 54-59 15385826-2 2004 Likewise, sirolimus is a substrate for the major drug-metabolizing enzyme cytochrome P450 3A4 (CYP3A4) and the efflux transporter P-glycoprotein (P-gp), both of which are expressed in close proximity in epithelial cells lining the small intestine. Sirolimus 10-19 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 74-93 15385826-2 2004 Likewise, sirolimus is a substrate for the major drug-metabolizing enzyme cytochrome P450 3A4 (CYP3A4) and the efflux transporter P-glycoprotein (P-gp), both of which are expressed in close proximity in epithelial cells lining the small intestine. Sirolimus 10-19 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 95-101 15385826-4 2004 Modified Caco-2 cells metabolized [14C]sirolimus to the same CYP3A4-mediated metabolites as human small intestinal and liver microsomes. Sirolimus 39-48 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 61-67 15385826-10 2004 Along with CYP3A4-mediated metabolism and P-gp-mediated efflux, a novel elimination pathway was identified that may also contribute to the first-pass extraction, and hence low oral bioavailability, of sirolimus. Sirolimus 201-210 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 11-17 14529371-4 2003 We have demonstrated that the interplay between P-gp and CYP3A4 at the apical intestinal membrane can increase the opportunity for drug metabolism by determining bidirectional extraction ratios across CYP3A4 transfected Caco-2 cells for two dual P-gp/CYP3A4 substrates, K77 (an experimental cysteine protease inhibitor) and sirolimus, as well as two negative control, CYP3A4 only substrates, midazolam and felodipine. Sirolimus 324-333 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 57-63 14529371-4 2003 We have demonstrated that the interplay between P-gp and CYP3A4 at the apical intestinal membrane can increase the opportunity for drug metabolism by determining bidirectional extraction ratios across CYP3A4 transfected Caco-2 cells for two dual P-gp/CYP3A4 substrates, K77 (an experimental cysteine protease inhibitor) and sirolimus, as well as two negative control, CYP3A4 only substrates, midazolam and felodipine. Sirolimus 324-333 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 201-207 14529371-4 2003 We have demonstrated that the interplay between P-gp and CYP3A4 at the apical intestinal membrane can increase the opportunity for drug metabolism by determining bidirectional extraction ratios across CYP3A4 transfected Caco-2 cells for two dual P-gp/CYP3A4 substrates, K77 (an experimental cysteine protease inhibitor) and sirolimus, as well as two negative control, CYP3A4 only substrates, midazolam and felodipine. Sirolimus 324-333 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 201-207 14529371-4 2003 We have demonstrated that the interplay between P-gp and CYP3A4 at the apical intestinal membrane can increase the opportunity for drug metabolism by determining bidirectional extraction ratios across CYP3A4 transfected Caco-2 cells for two dual P-gp/CYP3A4 substrates, K77 (an experimental cysteine protease inhibitor) and sirolimus, as well as two negative control, CYP3A4 only substrates, midazolam and felodipine. Sirolimus 324-333 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 201-207 15307840-0 2004 CYP3A4 and P-glycoprotein activity in healthy controls and transplant patients on cyclosporin vs. tacrolimus vs. sirolimus. Sirolimus 113-122 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. Sirolimus 131-140 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. Sirolimus 131-140 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 224-230 15158963-2 2004 We have demonstrated that the interplay between P-gp and CYP3A4 at the apical intestinal membrane can increase the opportunity for drug metabolism by determining bidirectional extraction ratios across CYP3A4-transfected Caco-2 cells for two dual P-gp/CYP3A4 substrates, K77 (an experimental cysteine protease inhibitor) and sirolimus, as well as two negative control, CYP3A4 only substrates, midazolam and felodipine. Sirolimus 324-333 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 57-63 15158963-2 2004 We have demonstrated that the interplay between P-gp and CYP3A4 at the apical intestinal membrane can increase the opportunity for drug metabolism by determining bidirectional extraction ratios across CYP3A4-transfected Caco-2 cells for two dual P-gp/CYP3A4 substrates, K77 (an experimental cysteine protease inhibitor) and sirolimus, as well as two negative control, CYP3A4 only substrates, midazolam and felodipine. Sirolimus 324-333 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 201-207 15158963-2 2004 We have demonstrated that the interplay between P-gp and CYP3A4 at the apical intestinal membrane can increase the opportunity for drug metabolism by determining bidirectional extraction ratios across CYP3A4-transfected Caco-2 cells for two dual P-gp/CYP3A4 substrates, K77 (an experimental cysteine protease inhibitor) and sirolimus, as well as two negative control, CYP3A4 only substrates, midazolam and felodipine. Sirolimus 324-333 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 201-207 15158963-2 2004 We have demonstrated that the interplay between P-gp and CYP3A4 at the apical intestinal membrane can increase the opportunity for drug metabolism by determining bidirectional extraction ratios across CYP3A4-transfected Caco-2 cells for two dual P-gp/CYP3A4 substrates, K77 (an experimental cysteine protease inhibitor) and sirolimus, as well as two negative control, CYP3A4 only substrates, midazolam and felodipine. Sirolimus 324-333 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 201-207 14569063-0 2004 CYP3A4-transfected Caco-2 cells as a tool for understanding biochemical absorption barriers: studies with sirolimus and midazolam. Sirolimus 106-115 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 14569063-8 2004 Using CYP3A4-transfected Caco-2 cells we determined that, in contrast to P-gp, CYP3A4 is the major factor limiting sirolimus absorption. Sirolimus 115-124 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 6-12 14569063-8 2004 Using CYP3A4-transfected Caco-2 cells we determined that, in contrast to P-gp, CYP3A4 is the major factor limiting sirolimus absorption. Sirolimus 115-124 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 79-85 12469693-9 2002 Sirolimus is metabolised by the cytochrome P450 isoenzyme CYP3A4, so may induce drug interactions. Sirolimus 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 58-64 11907172-2 2002 Modified Caco-2 cells metabolized [(14)C]sirolimus to the predicted amounts of CYP3A4-mediated products based on CYP3A4 content, which was approximately 20% of that measured in human small intestinal mucosal homogenate. Sirolimus 41-50 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 79-85 11907172-2 2002 Modified Caco-2 cells metabolized [(14)C]sirolimus to the predicted amounts of CYP3A4-mediated products based on CYP3A4 content, which was approximately 20% of that measured in human small intestinal mucosal homogenate. Sirolimus 41-50 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 113-119 11907172-10 2002 Along with CYP3A4-mediated metabolism and P-gp-mediated secretion, we conclude that the following novel pathway, which occurs at least in the intestine, may contribute significantly to the first-pass extraction of sirolimus in humans: intracellular degradation of sirolimus to seco-rapamycin, metabolism of seco-rapamycin to M2 by an unidentified non-microsomal enzyme, and P-gp-mediated secretion of M2 and seco-rapamycin. Sirolimus 214-223 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 11-17 11180036-1 2001 AIM AND BACKGROUND: The pharmacokinetic interaction between sirolimus, a macrolide immunosuppressant metabolized by CYP3A4, and the calcium channel blocker diltiazem was studied in 18 healthy subjects. Sirolimus 60-69 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 116-122 11384247-0 2001 Metabolism of sirolimus and its derivative everolimus by cytochrome P450 3A4: insights from docking, molecular dynamics, and quantum chemical calculations. Sirolimus 14-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 57-76 11384247-1 2001 A combination of quantum chemical calculations and molecular simulations (DOCKing and molecular dynamics) is used to investigate the metabolism of sirolimus (rapamycin) and its derivative everolimus (SDZ-RAD) by cytochrome P450 3A4. Sirolimus 147-156 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 212-231 11384247-1 2001 A combination of quantum chemical calculations and molecular simulations (DOCKing and molecular dynamics) is used to investigate the metabolism of sirolimus (rapamycin) and its derivative everolimus (SDZ-RAD) by cytochrome P450 3A4. Sirolimus 158-167 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 212-231