PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 11038161-9 2000 Diltiazem, testosterone, and verapamil were metabolized predominantly by CYP3A4. Verapamil 29-38 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 73-79 11907487-12 2002 Consistent with expression data, formation of verapamil metabolites catalyzed by CYP3A4 and CYP2C was shown. Verapamil 46-55 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 81-87 11724091-7 2001 CYP3A4 is the main isoenzyme responsible for metabolism of erythromycin and verapamil. Verapamil 76-85 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 11724091-8 2001 Both drugs are potent inhibitors of CYP3A4 and of P-glycoprotein; this may be the basis for the pharmacokinetic interaction between erythromycin and verapamil. Verapamil 149-158 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 36-42 11318771-8 2001 Furthermore, the interaction of CBZ with drugs that modulate both CYP3A4 and Pgp function such as verapamil is probably due to inhibition of CYP3A4 and not Pgp. Verapamil 98-107 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 66-72 11318771-8 2001 Furthermore, the interaction of CBZ with drugs that modulate both CYP3A4 and Pgp function such as verapamil is probably due to inhibition of CYP3A4 and not Pgp. Verapamil 98-107 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 141-147 11498403-6 2000 A wealth of recent experimental data shows that many of the previously tested P-glycoprotein inhibitors, including verapamil, cyclosporin A, and valspodar (SDZ PSC 833), are substrates and/or potent inhibitors of cytochrome P450 3A4 (CYP3A4). Verapamil 115-124 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 213-232 11498403-6 2000 A wealth of recent experimental data shows that many of the previously tested P-glycoprotein inhibitors, including verapamil, cyclosporin A, and valspodar (SDZ PSC 833), are substrates and/or potent inhibitors of cytochrome P450 3A4 (CYP3A4). Verapamil 115-124 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 234-240 12036391-7 2002 The often-described higher hepatic clearance in women compared with men for substrates of CYP3A and P-glycoprotein, such as erythromycin and verapamil, may be explained by increased intrahepatocellular substrate availability due to lower hepatic P-glycoprotein activity in women relative to men. Verapamil 141-150 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 90-95 11422004-3 2001 Kinetics of CYP3A4 inactivation by verapamil and diltiazem were determined using testosterone as the substrate. Verapamil 35-44 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 12-18 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. Verapamil 9-18 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 76-82 9663178-12 1998 CONCLUSIONS: Both verapamil and diltiazem considerably increase plasma buspirone concentrations, probably by inhibiting its CYP3A4-mediated first-pass metabolism. Verapamil 18-27 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 124-130 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%). Verapamil 151-160 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 76-81 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%). Verapamil 151-160 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. Verapamil 50-59 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. Verapamil 72-81 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. Verapamil 72-81 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 293-298 10417494-0 1999 The effect of ketoconazole on the jejunal permeability and CYP3A metabolism of (R/S)-verapamil in humans. Verapamil 79-94 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 59-64 10859149-6 2000 This suggests that in addition to the impaired clearance mechanisms for verapamil, which are thought to be primarily mediated by CYP3A, biotransformation processes distal to the formation of norverapamil and D-617 are impaired as well. Verapamil 72-81 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 129-134 11741214-5 1999 In contrast, the IC50of CYP3A4 function, determined by examining the inhibition of the metabolism of midazolam by intestinal and liver microsomes, was in the order L-754,384 < ketoconazole << PSC 833 and verapamil. Verapamil 213-222 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 24-30 11741214-6 1999 The ratio of IC50for P-gp to that for CYP3A4 was more than 200 for L-754,394, 60 ~ 150 for ketoconazole, 1.5 for verapamil, and 0.05 for PSC 833. Verapamil 113-122 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 38-44 34495458-8 2021 The model predicted that co-administration of various moderate CYP3A4 inhibitors (verapamil, erythromycin, clarithromycin, fluconazole, and diltiazem) would result in an average increase in entrectinib exposure between 2.2- and 3.1-fold, with corresponding average increases for M5 of approximately 2-fold. Verapamil 82-91 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 63-69 9400033-2 1997 For some of these (e.g., cyclosporine, verapamil, midazolam), CYP3A in the intestinal mucosa contributes to their extensive and variable first-pass extraction. Verapamil 39-48 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 62-67 10837554-13 1997 It is also clear that some of the substrates for CYP3A4 (e.g., cyclosporine, midazolam, nifedipine, verapamil and saquinavir) undergo significant metabolic extraction by the gut wall. Verapamil 100-109 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 49-55 8861661-6 1996 In addition, in healthy volunteers and cancer patients, the N-demethylation of DM correlated with the CYP3A-mediated metabolism of verapamil and tamoxifen. Verapamil 131-140 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 102-107 8232610-9 1993 Formation of D-617 was correlated with the expression of CYP3A (r = 0.85; P < 0.001) and CYP1A2 (r = 0.57; P < 0.01) in the microsomal fraction of 21 human livers after incubation with racemic verapamil. Verapamil 199-208 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 57-62 8423765-11 1993 Verapamil (substrate of CYP3A4 and CYP1A2) and midazolam (substrate of CYP3A4) were competitive inhibitors of N-desalkylpropafenone formation (Ki = 70 microM and 25 microM for verapamil and midazolam, respectively). Verapamil 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 24-30 8423765-11 1993 Verapamil (substrate of CYP3A4 and CYP1A2) and midazolam (substrate of CYP3A4) were competitive inhibitors of N-desalkylpropafenone formation (Ki = 70 microM and 25 microM for verapamil and midazolam, respectively). Verapamil 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 71-77 8423765-11 1993 Verapamil (substrate of CYP3A4 and CYP1A2) and midazolam (substrate of CYP3A4) were competitive inhibitors of N-desalkylpropafenone formation (Ki = 70 microM and 25 microM for verapamil and midazolam, respectively). Verapamil 176-185 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 24-30 8423765-11 1993 Verapamil (substrate of CYP3A4 and CYP1A2) and midazolam (substrate of CYP3A4) were competitive inhibitors of N-desalkylpropafenone formation (Ki = 70 microM and 25 microM for verapamil and midazolam, respectively). Verapamil 176-185 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 71-77 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. Verapamil 73-82 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 108-114 32560124-1 2020 The calcium channel blocker and antiarrhythmic agent verapamil is recommended by the FDA for drug-drug interaction (DDI) studies as a moderate clinical CYP3A4 index inhibitor and as a clinical Pgp inhibitor. Verapamil 53-62 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 152-158 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. Verapamil 277-286 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. Verapamil 277-286 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 259-265 32560124-5 2020 The processes implemented to describe the pharmacokinetics of verapamil and norverapamil include enantioselective plasma protein binding, enantioselective metabolism by CYP3A4, non-stereospecific Pgp transport, and passive glomerular filtration. Verapamil 62-71 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 169-175 29523051-4 2019 Verapamil"s inhibition of both permeability-glycoprotein (P-gp) and CYP3A4 is suspected to have led to the adverse side effects seen in our patient. Verapamil 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 68-74 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. Verapamil 0-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 91-97 31506301-9 2019 Retrospective drug-drug interaction (DDI) simulations, incorporating in vitro metabolic inhibitory parameters, accurately recapitulated clinically observed attenuation of rivaroxaban"s hepatic clearance due to enzyme-mediated DDIs with CYP3A4/2J2 inhibitors (verapamil and ketoconazole). Verapamil 259-268 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 236-242 31089348-4 2019 Adding verapamil (100 muM), valspodar (5 muM) and ketoconazole (10 muM) significantly enhanced the permeability of REG across mucosal to serosal in the rat jejunum (P < 0.05) suggesting role of CYP 3A4 and/or efflux transporters in oral bioavailability of REG. Verapamil 7-16 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 197-204 29785610-10 2018 Troleandomycin and verapamil displayed quasi-irreversible MDI of CYP3A4; MIC formation was observed, while no formation of CYP-dependent GSH adducts occurred. Verapamil 19-28 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 65-71 27402157-6 2017 Using this final PBPK model, it was predicted that weak CYP3A inhibitors (fluoxetine and fluvoxamine) are anticipated to have negligible DDI risk with palbociclib, whereas moderate CYP3A inhibitors (diltiazem and verapamil) may increase plasma palbociclib AUC by ~40%. Verapamil 213-222 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 56-61 27939799-4 2017 The selective P-gp inhibitors (CP100356 and PSC833) enhanced 3-hydroxy-quinidine (3OH-Qi) in jejunum and ileum, while dual inhibitors of P-gp and CYP3A4 (verapamil and ketoconazole) decreased the 3OH-Qi production, despite of the increased intracellular Qi concentration, due to inhibition of CYP3A4. Verapamil 154-163 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 146-152 27538919-6 2016 The best predictability of FaFg was achieved when considering both SFCYP3A and SFP-gp The simulation also clarified the relative importance of CYP3A and P-gp in determining FaFg In particular, the nonlinear intestinal absorption of verapamil was caused by the saturation of intestinal CYP3A, whereas that of quinidine was governed by the saturation of both CYP3A and P-gp. Verapamil 232-241 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 69-74 27538919-6 2016 The best predictability of FaFg was achieved when considering both SFCYP3A and SFP-gp The simulation also clarified the relative importance of CYP3A and P-gp in determining FaFg In particular, the nonlinear intestinal absorption of verapamil was caused by the saturation of intestinal CYP3A, whereas that of quinidine was governed by the saturation of both CYP3A and P-gp. Verapamil 232-241 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 143-148 27538919-6 2016 The best predictability of FaFg was achieved when considering both SFCYP3A and SFP-gp The simulation also clarified the relative importance of CYP3A and P-gp in determining FaFg In particular, the nonlinear intestinal absorption of verapamil was caused by the saturation of intestinal CYP3A, whereas that of quinidine was governed by the saturation of both CYP3A and P-gp. Verapamil 232-241 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 143-148 26813987-2 2016 We report a serious side effect of ibrutinib potentially attributable to interaction with the moderate CYP3A4 inhibitor verapamil. Verapamil 120-129 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 103-109 27627192-8 2016 Simcyp predicted the effects of ketoconazole and verapamil on the sensitive CYP3A4 substrate AZD1305 pharmacokinetics well. Verapamil 49-58 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 76-82 26813987-9 2016 WHAT IS NEW AND CONCLUSION: This is the first description of a serious side effect of ibrutinib likely due to an interaction with the CYP3A4 inhibitor verapamil. Verapamil 151-160 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 134-140 25571292-2 2014 Verapamil and its active metabolite, norverapamil, are known to be CYP3A4 inhibitors. Verapamil 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 67-73 26301745-3 2015 Their bidirectional transports were significantly reduced by 75.6-87.5% after treatment with verapamil (a P-glycoprotein inhibitor) that increased the rate of metabolism by CYP3A4, whereas the CYP3A4 inhibitor ketoconazole treatment markedly enhanced the basolateral to apical flux of (-) and (+)CLA with ERs being 2.934+-1.432 and 1.877+-0.148(x10(-6)cm/s) respectively. Verapamil 93-102 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 173-179 26301745-3 2015 Their bidirectional transports were significantly reduced by 75.6-87.5% after treatment with verapamil (a P-glycoprotein inhibitor) that increased the rate of metabolism by CYP3A4, whereas the CYP3A4 inhibitor ketoconazole treatment markedly enhanced the basolateral to apical flux of (-) and (+)CLA with ERs being 2.934+-1.432 and 1.877+-0.148(x10(-6)cm/s) respectively. Verapamil 93-102 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 193-199 26301745-4 2015 These changes could be blocked by the duel CYP3A4/P-glycoprotein inhibitor cyclosporine A, consequently, Papp values for CLA enantiomers in both directions were significantly greater than those obtained by using verapamil or ketoconazole, and their ERs were similar to those following (-) or (+)-isomer treatment alone. Verapamil 212-221 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 43-49 25571292-3 2014 Co-administration of verapamil with CYP3A4 substrates can alter the pharmacokinetics of the substrates. Verapamil 21-30 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 36-42 23916407-1 2013 Verapamil and its major metabolite norverapamil were identified to be both mechanism-based inhibitors and substrates of CYP3A and reported to have non-linear pharmacokinetics in clinic. Verapamil 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 120-125 23916407-8 2013 Finally, the developed semi-PBPK model was further applied to predict drug-drug interactions (DDI) between verapamil and other three CYP3A substrates including midazolam, simvastatin, and cyclosporine A. Verapamil 107-116 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 133-138 23916407-3 2013 The results showed that S-isomers were more preferential to be metabolized than R-isomers for both verapamil and norverapamil, and their inhibitory effects on CYP3A activity were also stereoselective with S-isomers more potent than R-isomers. Verapamil 99-108 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 159-164 23751364-5 2013 Consequently, slight enantioselectivity was found for the CYP3A4 metabolism of verapamil. Verapamil 79-88 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 58-64 23188647-4 2013 Comparing results obtained from a known CYP3A4 inhibitor, verapamil, the flavonoids inhibited felodipine metabolism. Verapamil 58-67 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 40-46 19255936-9 2009 Slow acting inhibitors (such as verapamil/CYP3A4 or S-fluoxetine/CYP2C19) showed an increase in IC(50) shift between 10 and 30 min suggesting a longer maximum pre-incubation time with wider spacing of time points for K(I)/k(inact). Verapamil 32-41 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 42-48 21447389-4 2011 This was done by using human substrates of CYP3A4 (verapamil and testosterone), CYP2C9 (diclofenac) and CYP2D6 (dextromethorphan). Verapamil 51-60 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 43-49 21832258-3 2011 In the 384-well plate CYP3A4 inhibition assay, the known inhibitors 1-aminobenzotriazole, erythromycin, ketoconazole, and verapamil were found to cause extensive (maximum inhibition of >80%), dose-dependent, statistically significant inhibition of LIPA metabolism. Verapamil 122-131 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 22-28 21716273-3 2011 Verapamil and quinidine are good substrates of both the multidrug resistance 1 transporter (MDR1) and the cytochrome P450 (CYP) 3A4 enzyme (CYP3A4). Verapamil 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 140-146 20214408-0 2010 Predictions of metabolic drug-drug interactions using physiologically based modelling: Two cytochrome P450 3A4 substrates coadministered with ketoconazole or verapamil. Verapamil 158-167 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 91-110 20012601-2 2010 Verapamil is a substrate of both P-gp and CYP3A4. Verapamil 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 42-48 20012601-11 2010 CONCLUSION: Lovastatin increased the absorption of verapamil by inhibiting P-gp and inhibited the first-pass metabolism of verapamil by inhibiting CYP3A4 in the intestine and/or liver in humans. Verapamil 123-132 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 147-153 19444798-7 2009 The method has been successfully applied for the in vitro inhibition of metabolism of dextromethorphan by CYP2D6 and CYP3A4 using known inhibitors of CYPs such as quinidine and verapamil. Verapamil 177-186 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 117-123 19307295-2 2009 Over half of the compounds tested (14 of 24) were identified as time-dependent inhibitors of CYP3A4 and high mRNA/activity ratios (>10) were consistent with CYP3A4 time-dependent inhibition for compounds such as troleandomycin, ritonavir, and verapamil. Verapamil 246-255 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 93-99 19307295-2 2009 Over half of the compounds tested (14 of 24) were identified as time-dependent inhibitors of CYP3A4 and high mRNA/activity ratios (>10) were consistent with CYP3A4 time-dependent inhibition for compounds such as troleandomycin, ritonavir, and verapamil. Verapamil 246-255 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 160-166 19280517-3 2009 Atorvastatin and verapamil have interesting clinical pharmacology attributes in that both agents are substrates and/or inhibitors of the dual cytochrome P450 (CYP) 3A4 and P-glycoprotein (Pgp) efflux transporter interplay. Verapamil 17-26 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 142-167 18661126-0 2008 Dual drug interactions via P-glycoprotein (P-gp)/ cytochrome P450 (CYP3A4) interplay: recent case study of oral atorvastatin and verapamil. Verapamil 129-138 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 67-73 18193210-8 2008 CONCLUSION: The above data suggest that atorvastatin could inhibit the absorption of verapamil via inhibition of P-gp and/or the metabolism of verapamil by CYP3A4 in humans. Verapamil 85-94 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 156-162 18559486-9 2008 Stimulation with 3-methylcholanthrene and rifampicin markedly increased CYP1A1/2 or CYP3A4 activities, which could be selectively inhibited by nifedipine, verapamil, ketoconazole, and quercetin. Verapamil 155-164 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 84-90 18193210-1 2008 AIM: It has been reported that verapamil and atorvastatin are inhibitors of both P-glycoprotein (P-gp) and microsomal cytochrome P450 (CYP) 3A4, and verapamil is a substrate of both P-gp and CYP3A4. Verapamil 31-40 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 118-143 18193210-8 2008 CONCLUSION: The above data suggest that atorvastatin could inhibit the absorption of verapamil via inhibition of P-gp and/or the metabolism of verapamil by CYP3A4 in humans. Verapamil 143-152 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 156-162 18193210-1 2008 AIM: It has been reported that verapamil and atorvastatin are inhibitors of both P-glycoprotein (P-gp) and microsomal cytochrome P450 (CYP) 3A4, and verapamil is a substrate of both P-gp and CYP3A4. Verapamil 31-40 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 191-197 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. Verapamil 177-186 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 109-114 16892180-9 2006 These observations indicate that the elimination rate of verapamil is faster in women than men which may be attributed to the higher activity of CYP3A4 or lower activity of P-glycoprotein in women compared with men. Verapamil 57-66 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 145-151 17178259-5 2006 Weak or moderately potent CYP3A4 inhibitors (eg, verapamil and diltiazem) can be used cautiously with small doses of CYP3A4-dependent statins. Verapamil 49-58 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. Verapamil 49-58 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 117-123 16187976-1 2005 AIMS: We sought to define the influence of verapamil, an inhibitor of CYP3A and P-glycoprotein, on the pharmacokinetics of everolimus, a substrate of this enzyme and transporter. Verapamil 43-52 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 70-75 16376901-0 2006 Chiral capillary electrophoretic analysis of verapamil metabolism by cytochrome P450 3A4. Verapamil 45-54 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 69-88 16376901-5 2006 Verapamil was chosen as the substrate for CYP 3A4 isozyme (Supersome). Verapamil 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 42-49 16513446-1 2006 BACKGROUND: Verapamil has the capability to inhibit and induce cytochrome P450 (CYP) 3A and P-glycoprotein (P-gp), but the relative extent and time course of these events in vivo are unclear. Verapamil 12-21 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 63-87 16513446-2 2006 The effect of verapamil on CYP3A and P-gp activity was determined by examining its effect on its own disposition and on the disposition of fexofenadine, respectively. Verapamil 14-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 27-32 16513446-12 2006 CONCLUSION: Verapamil inhibited CYP3A activity, with a maximum effect occurring within 10 days. Verapamil 12-21 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 32-37 15001968-9 2004 Values for the maximum rate of metabolism (V(max)) of verapamil N-dealkylation (formation of D-617) and N-demethylation (formation of norverapamil) activities correlated with the CYP3A4 protein content in both organs. Verapamil 54-63 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 179-185 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. Verapamil 14-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 129-135 15689501-4 2005 The possibility that verapamil and its metabolites form metabolic-intermediate complex (MIC) with CYP3A was assessed using dual beam spectrophotometry. Verapamil 21-30 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 98-103 15689501-10 2005 These findings indicate that the presence of variable CYP3A5/CYP3A4 expression in the liver may contribute to the interindividual variability associated with verapamil-mediated drug interactions. Verapamil 158-167 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 61-67 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. Verapamil 15-24 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 160-179 15692829-1 2005 OBJECTIVE: To investigate the effect of acute hypoxia and concomitant changes in portal blood flow on the disposition of drugs mainly metabolized by the cytochrome P(450) enzymes (CYP) 3A4 (verapamil) and CYP1A2 (theophylline). Verapamil 190-199 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 153-188 15905061-0 2005 Kinetic study of CYP3A4 activity on verapamil by capillary electrophoresis. Verapamil 36-45 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 17-23 15905061-1 2005 The use of capillary electrophoresis (CE) for the determination of CYP3A4 activity with verapamil as a substrate was investigated. Verapamil 88-97 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 67-73 15689501-0 2005 Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Verapamil 64-73 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 43-49 15689501-2 2005 The purpose of this study is to quantify the capability of verapamil, a mechanism-based inhibitor of CYP3A, and its metabolites to inhibit the activities of CYP3A4 and CYP3A5, and to determine whether CYP3A5 expression in human liver microsomes alters the inhibitory potency of verapamil. Verapamil 59-68 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 101-106 15689501-2 2005 The purpose of this study is to quantify the capability of verapamil, a mechanism-based inhibitor of CYP3A, and its metabolites to inhibit the activities of CYP3A4 and CYP3A5, and to determine whether CYP3A5 expression in human liver microsomes alters the inhibitory potency of verapamil. Verapamil 59-68 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 157-163 15689501-2 2005 The purpose of this study is to quantify the capability of verapamil, a mechanism-based inhibitor of CYP3A, and its metabolites to inhibit the activities of CYP3A4 and CYP3A5, and to determine whether CYP3A5 expression in human liver microsomes alters the inhibitory potency of verapamil. Verapamil 278-287 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 101-106 15689501-2 2005 The purpose of this study is to quantify the capability of verapamil, a mechanism-based inhibitor of CYP3A, and its metabolites to inhibit the activities of CYP3A4 and CYP3A5, and to determine whether CYP3A5 expression in human liver microsomes alters the inhibitory potency of verapamil. Verapamil 278-287 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 157-163 15676042-9 2005 Ex vivo incubation of enterocyte homogenates with verapamil resulted in a significantly increased production of the metabolites formed via CYP3A4 (D-617: 125.9 +/- 118.8 vs. 277.2 +/- 145.5 pmol min(-1) mg(-1) protein (P < 0.05, 95% CI: 30.1-272.5); norverapamil: 113.0 +/- 57.9 vs. 398.4 +/- 148.2 pmol min(-1) mg(-1) protein (P < 0.05, 95% CI: 47.2-523.6)). Verapamil 50-59 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 139-145 15371984-9 2004 Moreover, intrinsic clearance of CYP3A4-mediated verapamil metabolism in homogenates of simultaneously collected shed enterocytes correlated with in vivo E GI of d0-verapamil 15 min /d3-verapamil 240 min (r = 0.62, P =.03). Verapamil 49-58 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 33-39 15371984-9 2004 Moreover, intrinsic clearance of CYP3A4-mediated verapamil metabolism in homogenates of simultaneously collected shed enterocytes correlated with in vivo E GI of d0-verapamil 15 min /d3-verapamil 240 min (r = 0.62, P =.03). Verapamil 165-174 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 33-39 15277015-8 2004 Typical CYP3A4 substrates, such as midazolam, testosterone, nifedipine and verapamil, are shown to fit the putative active site of the enzyme structure in a manner consistent with their known positions of metabolism. Verapamil 75-84 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 8-14 14744949-3 2004 The values of the inactivation kinetic parameters kinact and KI obtained with the cDNA-expressed CYP3A4 (+b5) were 0.39 min(-1) and 6.46 microM for R-verapamil, 0.64 min(-1) and 2.97 microM for S-verapamil, 1.12 min(-1) and 5.89 microM for (+/-)-norverapamil, and 0.07 min(-1) and 7.93 microM for D617. Verapamil 148-159 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 97-103 14744940-1 2004 In vitro studies of enantioselective metabolism of R-(+)- and S-(-)verapamil (VER) were conducted using human cDNA-expressed CYP3A isoforms, CYP3A4, CYP3A5, and CYP3A7. Verapamil 62-76 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 125-130 14744949-3 2004 The values of the inactivation kinetic parameters kinact and KI obtained with the cDNA-expressed CYP3A4 (+b5) were 0.39 min(-1) and 6.46 microM for R-verapamil, 0.64 min(-1) and 2.97 microM for S-verapamil, 1.12 min(-1) and 5.89 microM for (+/-)-norverapamil, and 0.07 min(-1) and 7.93 microM for D617. Verapamil 194-205 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 97-103 14744949-1 2004 Verapamil inhibition of CYP3A activity results in many drug-drug interactions with CYP3A substrates, but the mechanism of inhibition is unclear. Verapamil 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 24-29 14744949-7 2004 A mechanism-based pharmacokinetic model predicted that the oral area under the curve (AUC) of a CYP3A substrate that is eliminated completely (fm=1) by the hepatic CYP3A increased 1.6- to 2.2-fold after repeated oral administration of verapamil. Verapamil 235-244 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 96-101 14744949-1 2004 Verapamil inhibition of CYP3A activity results in many drug-drug interactions with CYP3A substrates, but the mechanism of inhibition is unclear. Verapamil 0-9 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 83-88 14744949-7 2004 A mechanism-based pharmacokinetic model predicted that the oral area under the curve (AUC) of a CYP3A substrate that is eliminated completely (fm=1) by the hepatic CYP3A increased 1.6- to 2.2-fold after repeated oral administration of verapamil. Verapamil 235-244 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 164-169 14744949-2 2004 The present study showed that verapamil enantiomers and their major metabolites [norverapamil and N-desalkylverapamil (D617)] inhibited CYP3A in a time- and concentration-dependent manner by using pooled human liver microsomes and the cDNA-expressed CYP3A4 (+b5). Verapamil 30-39 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 136-141 14744949-2 2004 The present study showed that verapamil enantiomers and their major metabolites [norverapamil and N-desalkylverapamil (D617)] inhibited CYP3A in a time- and concentration-dependent manner by using pooled human liver microsomes and the cDNA-expressed CYP3A4 (+b5). Verapamil 30-39 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 250-256 12130727-6 2002 Moreover, by using human liver microsomes we determined the effect of piperine on CYP3A4-mediated formation of the verapamil metabolites D-617 and norverapamil. Verapamil 115-124 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 82-88 14512885-3 2003 We investigated CYP3A4 in a large collection (n = 94) of well-characterized surgical liver samples and found 2-fold higher CYP3A4 levels in female compared with male samples (P <.0001) and a corresponding 50% increase in the CYP3A-dependent N-dealkylation of verapamil (P <.01). Verapamil 262-271 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 123-129 12781333-5 2003 Addition of CYP3A4 substrates (verapamil, midazolam, quinidine, and progesterone) to the oxygenated solution caused a concentration-dependent increase in the reduction current in cyclic voltammetric and amperometric experiments. Verapamil 31-40 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 12-18 12729862-0 2003 Enantioselective transport and CYP3A4-mediated metabolism of R/S-verapamil in Caco-2 cell monolayers. Verapamil 65-74 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 31-37 12729862-1 2003 We have evaluated the passive and carrier-mediated intestinal transport and CYP3A4-mediated metabolism of R/S-verapamil with respect to dose dependency and enantioselectivity in modified Caco-2 cells. Verapamil 110-119 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 76-82