PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 32803289-1 2021 PURPOSE: To evaluate the role of diltiazem on tacrolimus sparing in pediatric primary nephrotic syndrome (PNS) and its relation to CYP3A4, CYP3A5, ABCB1, and SLCO1B3 polymorphisms. Diltiazem 33-42 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 131-137 33666764-6 2021 Data has established the calcium channel blockers, namely, diltiazem and verapamil, as potent inhibitors of CYP3A4, and the majority of significant drug interactions involving antihypertensives are attributable to these two agents. Diltiazem 59-68 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 108-114 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. Diltiazem 31-40 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 107-113 32080863-10 2020 The PBPK model predicted 3.78- and 7.15-fold increases in the AUC of the potency-adjusted unbound active species with strong CYP3A4 inhibitors itraconazole and ketoconazole, respectively; and 1.62- and 2.37-fold increases with the concomitant use of moderate CYP3A4 inhibitors verapamil and diltiazem, respectively. Diltiazem 291-300 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 125-131 32080863-10 2020 The PBPK model predicted 3.78- and 7.15-fold increases in the AUC of the potency-adjusted unbound active species with strong CYP3A4 inhibitors itraconazole and ketoconazole, respectively; and 1.62- and 2.37-fold increases with the concomitant use of moderate CYP3A4 inhibitors verapamil and diltiazem, respectively. Diltiazem 291-300 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 259-265 24604243-0 2014 Pharmacokinetic interactions between the orexin receptor antagonist almorexant and the CYP3A4 inhibitors ketoconazole and diltiazem. Diltiazem 122-131 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 87-93 30284597-5 2019 RESULTS: Moderate CYP3A4 inhibition by diltiazem (240 mg/day) increased the Cmax and AUC0- of ACT-541468 by 1.4-fold (90% confidence interval (CI): 1.2-1.6) and 2.4-fold (90% CI: 2.0-2.8), respectively, and prolonged t1/2 by 80% (90% CI: 60-90) without affecting tmax. Diltiazem 39-48 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 18-24 27149910-10 2016 WHAT IS NEW AND CONCLUSION: The CYP3A4*1G and CYP3A5*3 genetic polymorphisms are closely related to the trough concentration/dose ratios and pharmacokinetics of diltiazem and its main metabolites in Chinese adult renal transplant patients. Diltiazem 161-170 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 32-38 32329770-3 2020 Verapamil hydrochloride and diltiazem hydrochloride are combined P-glycoprotein (P-gp) and CYP3A4 inhibitors and may be associated with increases in the risk of bleeding with DOACs. Diltiazem 28-51 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 91-97 30099888-1 2019 BACKGROUND: It is unknown whether diltiazem, a moderate cytochrome P450 enzyme (CYP3A4) and P-glycoprotein (P-gp) inhibitor, increases the incidence of bleeding events in combination with rivaroxaban, a CYP3A4 and P-gp substrate. Diltiazem 34-43 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 80-86 29728928-0 2018 Effects of diltiazem, a moderate inhibitor of CYP3A4, on the pharmacokinetics of tamsulosin in different CYP2D6 genotypes. Diltiazem 11-20 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 46-52 29728928-2 2018 In this study, we investigated the effects of diltiazem, a moderate inhibitor of CYP3A4, on the pharmacokinetics of tamsulosin in subjects with different CYP2D6 genotypes. Diltiazem 46-55 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 81-87 27191770-8 2016 DISCUSSION: Because suvorexant is metabolized by CYP3A4, next-day somnolence could have occurred as a result of increased plasma suvorexant concentration due to CYP3A4 inhibition by diltiazem. Diltiazem 182-191 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 161-167 27149910-0 2016 Significant impacts of CYP3A4*1G and CYP3A5*3 genetic polymorphisms on the pharmacokinetics of diltiazem and its main metabolites in Chinese adult kidney transplant patients. Diltiazem 95-104 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 23-29 27149910-3 2016 This study was carried out to investigate the impacts of the CYP3A4*1G and CYP3A5*3 genetic polymorphisms on the trough concentration/dose ratios and pharmacokinetics of diltiazem and its main metabolites in Chinese adult renal transplant patients. Diltiazem 170-179 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 61-67 27149910-7 2016 RESULTS AND DISCUSSION: The dose-adjusted concentrations and pharmacokinetics of diltiazem and its main metabolites were significantly affected by CYP3A4 *1G and CYP3A5*3 alleles. Diltiazem 81-90 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 147-153 27149910-8 2016 Patients with a CYP3A4*1/*1 genotype were found to have a higher dose-adjusted trough concentration and AUC of diltiazem and its main metabolites compared with those with CYP3A4*1G*1G(P<0 05). Diltiazem 111-120 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 16-22 27121666-7 2013 In conclusion, diltiazem markedly affected the pharmacokinetics of ACT-077825, probably via inhibition of CYP3A4 activity, without changing its safety and tolerability profile in healthy male subjects. Diltiazem 15-24 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 106-112 21835977-5 2011 Using two of the optimized methods, the time-dependent inhibition kinetic parameters (K(I) and k(inact)) for four known CYP3A4 TDI (diltiazem, erythromycin, verapamil, and troleandomycin) were determined. Diltiazem 132-141 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 120-126 23381958-2 2013 This study investigated the effect of diltiazem, a moderate inhibitor of CYP3A4, on the single-dose pharmacokinetics of ACT-178882 in healthy subjects. Diltiazem 38-47 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 73-79 22828972-13 2012 Enzyme inhibition produced by diltiazem may have contributed to decreasing CYP3A4 activity. Diltiazem 30-39 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 75-81 22652334-7 2012 After pre-incubation, CYP3A4 IC(50) shifts caused by diltiazem and mifepristone were greater than 2.5- and 3.7-fold, respectively. Diltiazem 53-62 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 22-28 22652334-8 2012 Incubation with 2mM potassium ferricyanide for 10min reversed the MDI of CYP3A4 by diltiazem, but not mifepristone. Diltiazem 83-92 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 73-79 22652334-10 2012 The established methods were confirmed using three CYP3A4 inhibitors including diltiazem, mifepristone and amiodarone (a reversible metabolism-dependent inhibitor). Diltiazem 79-88 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 51-57 21480191-2 2011 Seven separate drug-drug interaction (DDI) studies were performed to elucidate the in vivo effects of concomitant treatment with colchicine and known inhibitors of cytochrome P450 3A4 (CYP3A4)/P-glycoprotein (cyclosporine, ketoconazole, ritonavir, clarithromycin, azithromycin, verapamil ER [extended release]), and diltiazem ER) on the pharmacokinetics of colchicine. Diltiazem 316-325 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 185-191 21209240-2 2011 Diltiazem interaction studies assess a given compound"s sensitivity to moderate CYP3A inhibition. Diltiazem 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 80-85 17304269-2 2007 Simvastatin interactions with warfarin and the cytochrome P450-3A4 inhibitor diltiazem were suspected as possible causes of the events (fatal intracranial haemorrhage with INR > 8 and myopathy). Diltiazem 77-86 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 47-66 21356216-3 2011 MAIN METHODS: Diltiazem N-demethylase activity of recombinant CYP3A4, CYP3A5, CYP3A7, and human liver microsomes (HLMs) in the presence of cannabinoids was determined. Diltiazem 14-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 62-68 22287853-6 2011 Mean exposure (AUC) of the CYP3A4-generated active metabolite of saxagliptin, 5-hydroxy saxagliptin, decreased with coadministration of simvastatin, diltiazem, and ketoconazole by 2%, 34%, and 88%, respectively. Diltiazem 149-158 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 27-33 21084035-4 2010 The possible relative risk factors included advanced age, chronic and systemic diseases, and co-administration of cytochrome P450 3A (CYP3A) enzyme-dependent metabolic drugs or its inhibitors such as clopidogrel and diltiazem. Diltiazem 216-225 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 114-132 21084035-4 2010 The possible relative risk factors included advanced age, chronic and systemic diseases, and co-administration of cytochrome P450 3A (CYP3A) enzyme-dependent metabolic drugs or its inhibitors such as clopidogrel and diltiazem. Diltiazem 216-225 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 134-139 19420129-1 2009 Prediction of the extent and time course of drug-drug interactions (DDIs) between the mechanism-based inhibitor diltiazem (DTZ) and the CYP3A4 substrate midazolam (MDZ) is confounded by time- and concentration-dependent clearance of the inhibitor. Diltiazem 112-121 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 136-142 19420129-1 2009 Prediction of the extent and time course of drug-drug interactions (DDIs) between the mechanism-based inhibitor diltiazem (DTZ) and the CYP3A4 substrate midazolam (MDZ) is confounded by time- and concentration-dependent clearance of the inhibitor. Diltiazem 123-126 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 136-142 19420129-3 2009 Enzyme kinetic parameters (k(inact) and K(I)) for DTZ and nd-DTZ were estimated in vitro and used to model the time course of changes in the amount of CYP3A4 in the liver and gut wall, which in turn, determined the nonlinear elimination of MDZ and DTZ, and the corresponding DDI. Diltiazem 50-53 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 151-157 19420129-3 2009 Enzyme kinetic parameters (k(inact) and K(I)) for DTZ and nd-DTZ were estimated in vitro and used to model the time course of changes in the amount of CYP3A4 in the liver and gut wall, which in turn, determined the nonlinear elimination of MDZ and DTZ, and the corresponding DDI. Diltiazem 61-64 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 151-157 19420129-9 2009 Moreover, model simulation suggested that both DTZ and nd-DTZ contributed to the overall inhibitory effect after DTZ administration, and the values of the in vitro estimated inhibition parameters and CYP3A4 turnover rate are critical for the prediction. Diltiazem 47-50 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 200-206 19420129-9 2009 Moreover, model simulation suggested that both DTZ and nd-DTZ contributed to the overall inhibitory effect after DTZ administration, and the values of the in vitro estimated inhibition parameters and CYP3A4 turnover rate are critical for the prediction. Diltiazem 58-61 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 200-206 18558792-8 2008 Diltiazem (86 events), verapamil (72), erythromycin (48) and clarithromycin (29) were the most commonly co-prescribed CYP3A4 inhibitors. Diltiazem 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 118-124 17293381-0 2007 Sequential metabolism is responsible for diltiazem-induced time-dependent loss of CYP3A. Diltiazem 41-50 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 82-87 17293381-2 2007 We previously reported that microsomal inactivation kinetic parameters of diltiazem underpredicted CYP3A inactivation in hepatocytes. Diltiazem 74-83 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 99-104 17293381-3 2007 In this study, we evaluated the contributions of inactivation and reversible inhibition of CYP3A by diltiazem and its N-desmethyl (MA) and N,N-didesmethyl (MD) metabolites. Diltiazem 100-109 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 91-96 17293381-6 2007 Inactivation of CYP3A by diltiazem was dependent on microsomal protein concentration (25, 36, and 41% decrease in CYP3A activity at 0.2, 0.4, and 0.8 mg/ml microsomal protein, respectively, incubated with 10 microM diltiazem over 20 min), whereas inactivation by MA did not seem to be protein concentration-dependent. Diltiazem 25-34 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 16-21 17293381-6 2007 Inactivation of CYP3A by diltiazem was dependent on microsomal protein concentration (25, 36, and 41% decrease in CYP3A activity at 0.2, 0.4, and 0.8 mg/ml microsomal protein, respectively, incubated with 10 microM diltiazem over 20 min), whereas inactivation by MA did not seem to be protein concentration-dependent. Diltiazem 25-34 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 114-119 17293381-6 2007 Inactivation of CYP3A by diltiazem was dependent on microsomal protein concentration (25, 36, and 41% decrease in CYP3A activity at 0.2, 0.4, and 0.8 mg/ml microsomal protein, respectively, incubated with 10 microM diltiazem over 20 min), whereas inactivation by MA did not seem to be protein concentration-dependent. Diltiazem 215-224 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 16-21 17293381-8 2007 In cryopreserved hepatocytes incubated with diltiazem, time-dependent loss of CYP3A was accompanied by increased formation of MA and MD, with the MA level similar to its K(I) at higher diltiazem concentrations. Diltiazem 44-53 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 78-83 17293381-8 2007 In cryopreserved hepatocytes incubated with diltiazem, time-dependent loss of CYP3A was accompanied by increased formation of MA and MD, with the MA level similar to its K(I) at higher diltiazem concentrations. Diltiazem 185-194 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 78-83 17293381-10 2007 In summary, time-dependent CYP3A inactivation by MA seems to be the major contributor responsible for the loss of CYP3A in human liver microsomes and human hepatocytes incubated with diltiazem. Diltiazem 183-192 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 27-32 17293381-10 2007 In summary, time-dependent CYP3A inactivation by MA seems to be the major contributor responsible for the loss of CYP3A in human liver microsomes and human hepatocytes incubated with diltiazem. Diltiazem 183-192 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 114-119 21112467-0 2010 Case report: delirium due to a diltiazem-fentanyl CYP3A4 drug interaction. Diltiazem 31-40 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 50-56 21112467-2 2010 Diltiazem inhibits cytochrome P450 3A4 isoenzymes. Diltiazem 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 19-38 20150526-1 2010 Diltiazem increases systemic exposure to simvastatin via inhibition of CYP3A. Diltiazem 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 71-76 18589174-12 2008 Coadministration of DTZ may further optimize the TAC level through preferential P-gp binding and CYP3A4 inhibition. Diltiazem 20-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 97-103 17392390-8 2007 In addition, we established an automated assay to distinguish quasi-irreversible and irreversible binding to CYP3A in which the quasi-irreversible inhibitors such as diltiazem, verapamil, and nicardipine were dissociated from CYP3A by the addition of potassium ferricyanide, whereas the irreversible inhibitors such as clozapine, delavirdine, and mibefradil were not. Diltiazem 166-175 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 109-114 17178259-5 2006 Weak or moderately potent CYP3A4 inhibitors (eg, verapamil and diltiazem) can be used cautiously with small doses of CYP3A4-dependent statins. Diltiazem 63-72 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 26-32 17178259-5 2006 Weak or moderately potent CYP3A4 inhibitors (eg, verapamil and diltiazem) can be used cautiously with small doses of CYP3A4-dependent statins. Diltiazem 63-72 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 117-123 15801939-0 2005 Diltiazem inhibits human intestinal cytochrome P450 3A (CYP3A) activity in vivo without altering the expression of intestinal mRNA or protein. Diltiazem 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 36-54 16640453-19 2006 Ranolazine AUC is increased by CYP3A inhibitors ranging from 1.5-fold for diltiazem 180 mg once daily to 3.9-fold for ketoconazole 200 mg twice daily. Diltiazem 74-83 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 31-36 16238231-7 2005 Diltiazem and verapamil are particularly prone to interactions, as they strongly inhibit the elimination of drugs undergoing the CYP3A4 and P-glycoprotein pathways. Diltiazem 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 129-135 15801939-1 2005 AIMS: To determine the effect of diltiazem on intestinal CYP3A activity and protein and mRNA expression in vivo in healthy subjects. Diltiazem 33-42 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 57-62 15801939-0 2005 Diltiazem inhibits human intestinal cytochrome P450 3A (CYP3A) activity in vivo without altering the expression of intestinal mRNA or protein. Diltiazem 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 56-61 15801939-7 2005 CONCLUSION: Diltiazem decreased small bowel CYP3A activity by 62% as a result of irreversible inhibition with no corresponding change in intestinal CYP3A4 mRNA or protein concentrations. Diltiazem 12-21 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 44-49 15858399-3 2005 CCBs are both substrates for, and in the instance of verapamil and diltiazem inhibitors of, cytochrome P450 3A4. Diltiazem 67-76 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 92-111 15858399-4 2005 In the case of verapamil and diltiazem, this inhibitory effect increases the likelihood of drug-drug interactions with other compounds similarly metabolized by cytochrome P450 3A4. Diltiazem 29-38 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 160-179 15377640-1 2004 The objectives of this study were to characterize and compare the reversible inhibition and time-dependent inactivation of cytochromes P450 3A4 and 3A5 (CYP3A4 and CYP3A5) by erythromycin, diltiazem, and nicardipine. Diltiazem 189-198 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 153-159 15304427-9 2004 Aprepitant was a moderate inhibitor of CYP3A4, with Ki values of approximately 10 microM for the 1"- and 4-hydroxylation of midazolam, and the N-demethylation of diltiazem, respectively. Diltiazem 162-171 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 39-45 15377640-11 2004 In conclusion, erythromycin, diltiazem, and nicardipine were weaker inhibitors of CYP3A5 and inactivated the enzyme at a slower rate than their respective effects on CYP3A4. Diltiazem 29-38 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 166-172 15370956-5 2004 Midazolam metabolism was also inhibited in vitro by typical chemical inhibitors of CYP3A, such as ketoconazole, erythromycin and diltiazem, and the apparent K(i) values for ketoconazole, erythromycin and diltiazem were 0.127, 94.2 and 29.6 microM, respectively. Diltiazem 129-138 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 83-88 15555475-13 2004 Concurrent use of inhibitors of the cytochrome P450 3A4 isozyme (eg, ketoconazole, diltiazem, cimetidine, atenolol) can significantly elevate serum concentrations of alfuzosin and enhance its pharmacodynamic effects. Diltiazem 83-92 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 36-55 11422004-3 2001 Kinetics of CYP3A4 inactivation by verapamil and diltiazem were determined using testosterone as the substrate. Diltiazem 49-58 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 12-18 11744603-1 2002 It has earlier been shown that the isoenzymes CYP2D6 and CYP3A4 are involved in O- and N-demethylation of diltiazem (DTZ), respectively. Diltiazem 106-115 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 57-63 11744603-1 2002 It has earlier been shown that the isoenzymes CYP2D6 and CYP3A4 are involved in O- and N-demethylation of diltiazem (DTZ), respectively. Diltiazem 117-120 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 57-63 11744603-2 2002 Apparently, CYP3A4 plays a more prominent role than CYP2D6 in the overall metabolism of DTZ. Diltiazem 88-91 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 12-18 11560871-0 2001 Effects of CYP3A4 inhibition by diltiazem on pharmacokinetics and dynamics of diazepam in relation to CYP2C19 genotype status. Diltiazem 32-41 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 11-17 11560871-3 2001 The aim of this study was to assess the effect of diltiazem, a CYP3A4 inhibitor, on pharmacokinetics and dynamics of diazepam in relation to CYP2C19 genotype status. Diltiazem 50-59 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 63-69 11560871-10 2001 Inhibition of CYP3A4 by a concomitant substrate drug like diltiazem may cause a pharmacokinetic interaction with diazepam irrespective of CYP2C19 genotype status, but whether this interaction would reflect a pharmacodynamic change of diazepam remains unconfirmed by our study. Diltiazem 58-67 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 14-20 12610742-5 2003 Fractions demonstrating significant CYP3A4 inhibitory activity, as measured by the relative reduction in N-demethylation of diltiazem in transfected human liver epithelial cells, were subsequently separated by preparative thin-layer chromatography. Diltiazem 124-133 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 36-42 12610742-8 2003 RESULTS: Of the identified components in grapefruit peel, only epoxybergamottin demonstrated a concentration-dependent inhibition of the CYP3A4-mediated N-demethylation of diltiazem. Diltiazem 172-181 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 137-143 11422004-12 2001 However, verapamil and diltiazem are moderate mechanism-based inhibitors of CYP3A4 and therefore may still cause significant inhibition of simvastatin metabolism in vivo during chronic therapy. Diltiazem 23-32 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 76-82 10741630-2 2000 Diltiazem is a substrate and an inhibitor of CYP3A enzymes and is commonly coadministered with cholesterol-lowering agents such as simvastatin. Diltiazem 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 45-50 11151747-5 2000 Metabolism of DTZ was studied over a concentration range of 12.5-400 microM and in the presence of quinidine (a CYP2D6 inhibitor) or erythromycin (a CYP3A4 inhibitor). Diltiazem 14-17 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 149-155 10971313-1 2000 AIMS: To study whether intravenous diltiazem, a calcium channel blocker commonly prescribed for hypertension and stable angina, is an inhibitor of the CYP3A enzymes by using oral lovastatin, an HMG Co-A reductase inhibitor, as a substrate. Diltiazem 35-44 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 151-156 11038161-9 2000 Diltiazem, testosterone, and verapamil were metabolized predominantly by CYP3A4. Diltiazem 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 73-79 10950845-2 2000 Rates for loss of CYP3A4 enzymatic activity resulting from metabolic intermediate complex formation and the concentration dependencies thereof were determined in vitro for clarithromycin, fluoxetine, and N-desmethyl diltiazem, which is the primary metabolite of diltiazem. Diltiazem 216-225 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 18-24 10950845-4 2000 Based on the predicted rates combined with published rates for in vivo CYP3A degradation, our model predicts that fluoxetine, clarithromycin, and the primary metabolite of diltiazem reduce the steady-state concentration of liver CYP3A4 to approximately 72, 39, or 21% of initial levels, respectively. Diltiazem 172-181 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 71-76 10950845-4 2000 Based on the predicted rates combined with published rates for in vivo CYP3A degradation, our model predicts that fluoxetine, clarithromycin, and the primary metabolite of diltiazem reduce the steady-state concentration of liver CYP3A4 to approximately 72, 39, or 21% of initial levels, respectively. Diltiazem 172-181 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 229-235 10950845-7 2000 The major implication of this work is that fluoxetine, clarithromycin, and the primary metabolite of diltiazem, at clinically relevant concentrations, inactivate CYP3A4 enzymatic activity at rates sufficient to affect in vivo concentrations of CYP3A4 and thereby affect the clearance of compounds eliminated by this pathway. Diltiazem 101-110 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 162-168 10950845-7 2000 The major implication of this work is that fluoxetine, clarithromycin, and the primary metabolite of diltiazem, at clinically relevant concentrations, inactivate CYP3A4 enzymatic activity at rates sufficient to affect in vivo concentrations of CYP3A4 and thereby affect the clearance of compounds eliminated by this pathway. Diltiazem 101-110 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 244-250 10741630-9 2000 CONCLUSION: Diltiazem coadministration resulted in a significant interaction with simvastatin, probably by inhibiting CYP3A-mediated metabolism. Diltiazem 12-21 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 118-123 10741630-10 2000 Concomitant use of diltiazem or other potent inhibitors of CYP3A with simvastatin should be avoided, or close clinical monitoring should be used. Diltiazem 19-28 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 59-64 10640508-7 2000 Unlike the observations with mibefradil, a potent irreversible inhibitor of CYP3A, the NADPH-dependent inhibition of CYP3A activity by nicardipine and verapamil was completely reversible on dialysis, whereas that by diltiazem was partially restored (80%). Diltiazem 216-225 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 117-122 10640508-8 2000 Additional experiments revealed that nicardipine, verapamil, and diltiazem formed cytochrome P-450-iron (II)-metabolite complex in both human liver microsomes and recombinant CYP3A4. Diltiazem 65-74 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 175-181 10640508-10 2000 These present findings that the CYP3A inhibition caused by nicardipine, verapamil, and diltiazem is, at least in part, quasi-irreversible provide a rational basis for pharmacokinetically significant interactions reported when they were coadministered with agents that are cleared primarily by CYP3A-mediated pathways. Diltiazem 87-96 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 32-37 10640508-10 2000 These present findings that the CYP3A inhibition caused by nicardipine, verapamil, and diltiazem is, at least in part, quasi-irreversible provide a rational basis for pharmacokinetically significant interactions reported when they were coadministered with agents that are cleared primarily by CYP3A-mediated pathways. Diltiazem 87-96 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 293-298 9663178-12 1998 CONCLUSIONS: Both verapamil and diltiazem considerably increase plasma buspirone concentrations, probably by inhibiting its CYP3A4-mediated first-pass metabolism. Diltiazem 32-41 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 124-130 10454485-1 1999 Diltiazem (DTZ) N-demethylation occurs by cytochrome P-450 (CYP) 3A based on the following observations: 1) a single enzyme Michaelis-Menten model of metabolite formation, 2) high correlations of DTZ N-demethylation activity to other CYP3A activities, 3) inhibition of DTZ N-demethylation activity by triacetyloleandomycin, and 4) DTZ N-demethylation activity by expressed CYP3A enzymes only. Diltiazem 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 42-67 10454485-1 1999 Diltiazem (DTZ) N-demethylation occurs by cytochrome P-450 (CYP) 3A based on the following observations: 1) a single enzyme Michaelis-Menten model of metabolite formation, 2) high correlations of DTZ N-demethylation activity to other CYP3A activities, 3) inhibition of DTZ N-demethylation activity by triacetyloleandomycin, and 4) DTZ N-demethylation activity by expressed CYP3A enzymes only. Diltiazem 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 234-239 10454485-1 1999 Diltiazem (DTZ) N-demethylation occurs by cytochrome P-450 (CYP) 3A based on the following observations: 1) a single enzyme Michaelis-Menten model of metabolite formation, 2) high correlations of DTZ N-demethylation activity to other CYP3A activities, 3) inhibition of DTZ N-demethylation activity by triacetyloleandomycin, and 4) DTZ N-demethylation activity by expressed CYP3A enzymes only. Diltiazem 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 373-378 10454485-1 1999 Diltiazem (DTZ) N-demethylation occurs by cytochrome P-450 (CYP) 3A based on the following observations: 1) a single enzyme Michaelis-Menten model of metabolite formation, 2) high correlations of DTZ N-demethylation activity to other CYP3A activities, 3) inhibition of DTZ N-demethylation activity by triacetyloleandomycin, and 4) DTZ N-demethylation activity by expressed CYP3A enzymes only. Diltiazem 11-14 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 42-67 10454485-1 1999 Diltiazem (DTZ) N-demethylation occurs by cytochrome P-450 (CYP) 3A based on the following observations: 1) a single enzyme Michaelis-Menten model of metabolite formation, 2) high correlations of DTZ N-demethylation activity to other CYP3A activities, 3) inhibition of DTZ N-demethylation activity by triacetyloleandomycin, and 4) DTZ N-demethylation activity by expressed CYP3A enzymes only. Diltiazem 11-14 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 234-239 10454485-1 1999 Diltiazem (DTZ) N-demethylation occurs by cytochrome P-450 (CYP) 3A based on the following observations: 1) a single enzyme Michaelis-Menten model of metabolite formation, 2) high correlations of DTZ N-demethylation activity to other CYP3A activities, 3) inhibition of DTZ N-demethylation activity by triacetyloleandomycin, and 4) DTZ N-demethylation activity by expressed CYP3A enzymes only. Diltiazem 11-14 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 373-378 10454485-3 1999 A 30-min preincubation of DTZ in expressed CYPs inhibited CYP3A4(+b(5)) by 100%, of which 55% was due to formation of a metabolite intermediate complex (MIC), which is an inactive form of CYP. Diltiazem 26-29 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 58-64 10454485-5 1999 In experiments to assess simultaneous MIC formation and loss of CYP3A activity, DTZ caused greater than 80% inhibition of midazolam hydroxylation after a 60-min preincubation in human liver microsomes. Diltiazem 80-83 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 64-69 10454485-7 1999 The mechanistic inhibition was characterized in expressed CYP3A4(+b(5)), which exhibited a concentration-dependent formation of MIC by DTZ (1-100 microM) with an estimated k(inact) of 0.17 min(-1) and K(I) of 2.2 microM. Diltiazem 135-138 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 58-64 10454485-9 1999 This study showed that DTZ inhibition of CYP3A substrate metabolism occurs primarily by MIC formation. Diltiazem 23-26 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 41-46 10410178-10 1999 Diltiazem inhibits CYP3A, P-glycoprotein, and tacrolimus metabolism in vitro. Diltiazem 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 19-24 10385214-12 1999 Diltiazem, erythromycin, nifedipine and cyclosporin (CYP 3A substrates) inhibited halofantrine metabolism. Diltiazem 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-59 9223567-7 1997 CYP3A4 in lymphoblastoid cell microsomes catalyzed DTZ N-demethylation but CYP2C8 and CYP2C9 were also active (approximately 20% and 10% of the activity supported by CYP3A4); seven other CYPs produced little or no N-desmethyl DTZ from DTZ. Diltiazem 51-54 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 9545159-3 1998 A possible drug interaction occurred in a 45-year-old woman who was taking cisapride for gastroesophageal reflux disorder and diltiazem, an agent that has inhibitory effect on CYP3A4, for hypertension. Diltiazem 126-135 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 176-182 9223567-0 1997 Role of CYP3A4 in human hepatic diltiazem N-demethylation: inhibition of CYP3A4 activity by oxidized diltiazem metabolites. Diltiazem 32-41 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 8-14 9223567-0 1997 Role of CYP3A4 in human hepatic diltiazem N-demethylation: inhibition of CYP3A4 activity by oxidized diltiazem metabolites. Diltiazem 101-110 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 73-79 9223567-8 1997 The CYP3A4 inhibitors ketoconazole and troleandomycin decreased microsomal DTZ oxidation, but inhibitors or substrates of CYP2C, CYP2D and CYP2E1 produced no inhibition. Diltiazem 75-78 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 4-10 9223567-11 1997 DTZ and its N-desmethyl and N,N-didesmethyl metabolites selectively inhibited CYP3A4 activity, whereas O-desmethyl DTZ was not inhibitory. Diltiazem 0-3 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 78-84 9223567-12 1997 The IC50 value of DTZ against CYP3A4-mediated testosterone 6beta-hydroxylation (substrate concentration, 50 microM) was 120 microM. Diltiazem 18-21 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 30-36 9223567-15 1997 CYP3A4 inhibition was enhanced when DTZ and N-desmethyl DTZ underwent biotransformation in NADPH-supplemented hepatic microsomes in vitro, supporting the contention that inhibitory metabolites may be generated in situ. Diltiazem 36-39 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 9223567-16 1997 These findings suggest that N-demethylated metabolites of DTZ may contribute to CYP3A4 inhibition in vivo, especially under conditions in which N-desmethyl DTZ accumulates, such as during prolonged DTZ therapy. Diltiazem 58-61 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 80-86 9223567-16 1997 These findings suggest that N-demethylated metabolites of DTZ may contribute to CYP3A4 inhibition in vivo, especially under conditions in which N-desmethyl DTZ accumulates, such as during prolonged DTZ therapy. Diltiazem 156-159 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 80-86 9146848-11 1997 Inhibition of CYP3A isozyme by diltiazem may explain the observed pharmacokinetic interaction. Diltiazem 31-40 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 14-19 35502121-2 2022 METHODS: A retrospective new-user cohort study design was used to identify (N=160828) patients who concurrently initiated CYP3A4-inhibitors (diltiazem, ketoconazole, clarithromycin, others) and CYP3A4-metabolized statins (statin DDI exposed, n = 104774) vs. other statins (unexposed to statin DDI, n = 56054) from the MarketScan Commercial claims database (2012 - 2017). Diltiazem 141-150 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 122-128 35386137-2 2022 We set out to compare the risk for hemorrhage following initiation of amiodarone, verapamil, or diltiazem (moderate cytochrome P450 3A4 and/or P-glycoprotein activity) vs metoprolol or amlodipine (weak or no activity), among older adults prescribed DOACs. Diltiazem 96-105 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 116-135