PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 34690774-0 2021 The Dynamic Effect of Non-CYP3A4-Metabolized and CYP3A4-Metabolized Statins on Clopidogrel Resistance in Patients With Cerebral Infarction. Clopidogrel 79-90 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 26-32 34690774-0 2021 The Dynamic Effect of Non-CYP3A4-Metabolized and CYP3A4-Metabolized Statins on Clopidogrel Resistance in Patients With Cerebral Infarction. Clopidogrel 79-90 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 49-55 35631502-0 2022 Physiologically Based Pharmacokinetic (PBPK) Modeling of Clopidogrel and Its Four Relevant Metabolites for CYP2B6, CYP2C8, CYP2C19, and CYP3A4 Drug-Drug-Gene Interaction Predictions. Clopidogrel 57-68 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 136-142 35631502-2 2022 Moreover, clopidogrel is a substrate of-among others-CYP2C19 and CYP3A4. Clopidogrel 10-21 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 65-71 31102151-1 2019 The objective of this study was to determine the impact of polymorphism of CYP3A subfamily isoenzymes (allelic variants of CYP3A4*22 and CYP3A5*3) on the efficacy clopidogrel in patients with an acute coronary syndrome (ACS), who have undergone percutaneous coronary intervention (PCI). Clopidogrel 163-174 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 123-129 32970826-4 2021 Drugs that are CYP2C19 or CYP3A4 inhibitors may reduce the effectiveness of clopidogrel and should be carefully considered during co-administration. Clopidogrel 76-87 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 26-32 33931001-3 2021 In contrast, carriers of CYP2C19*17, CYP3A4*1G, and CYP1A2*1F alleles showed a more significant antiplatelet effect in clopidogrel users and expected to have a protective role as a genetic factor against cardiovascular events. Clopidogrel 119-130 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 37-43 33270185-5 2021 METHODS: The effect of CYP2C19, CYP3A4/5, ABCB1 and PON1 genes on the plasma inactive metabolite concentration of clopidogrel and the platelet aggregation was investigated in 155 patients before and after PCI. Clopidogrel 114-125 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 32-40 33519456-9 2020 Clopidogrel resistance by DM was the integrated effects of altered K t,i, CYP2C19, CYP3A4, CES1 and k irre. Clopidogrel 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 83-89 32932966-0 2020 Effect of CYP3A4*22 and PPAR-alpha Genetic Variants on Platelet Reactivity in Patients Treated with Clopidogrel and Lipid-Lowering Drugs Undergoing Elective Percutaneous Coronary Intervention. Clopidogrel 100-111 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 10-16 32932966-1 2020 This study aims to determine whether genetic variants that influence CYP3A4 expression are associated with platelet reactivity in clopidogrel-treated patients undergoing elective percutaneous coronary intervention (PCI), and to evaluate the influence of statin/fibrate co-medication on these associations. Clopidogrel 130-141 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 69-75 30993551-1 2019 BACKGROUND AND OBJECTIVES: A recent report indicated that the pharmacodynamic interaction between clopidogrel and vonoprazan leading to attenuation of the anti-platelet effect of clopidogrel was unlikely to be caused by the inhibition of cytochrome P450 (CYP) 2B6, CYP2C19, or CYP3A4/5 by vonoprazan, based on in vitro CYP inhibition data. Clopidogrel 98-109 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 277-285 30648733-1 2019 Simultaneous competition for cytochrome P450 (CYP) 2C19 and CYP3A4 might diminish clopidogrel"s antiplatelet effect by impacting its metabolic activation. Clopidogrel 82-93 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 60-66 30648733-2 2019 This pharmacoepidemiologic study investigated whether proton pump inhibitors (PPIs) and CYP3A4-metabolized statins individually and jointly increase thrombotic events by attenuating clopidogrel"s effectiveness. Clopidogrel 182-193 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 88-94 29696643-2 2019 Ritonavir and clopidogrel are inhibitors of CYP3A4 and CYP2C8, respectively. Clopidogrel 14-25 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 44-50 30361928-2 2019 Clopidogrel is metabolized to the pharmacologically active metabolite H4 and its isomers by multiple CYPs, including CYP2C19 and CYP3A4. Clopidogrel 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 129-135 29998574-1 2019 CYP3A enzymes participate in the elimination of ticagrelor and the bioactivation of clopidogrel and prasugrel. Clopidogrel 84-95 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-5 30609441-1 2019 Amlodipine has a potential to reduce clopidogrel bioactivation through the cytochrome P450 3A4 enzyme in vivo, but the clinical impact of this interaction remains controversial. Clopidogrel 37-48 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 75-94 28875498-3 2018 CYP2C19 and CYP3A4 are involved in the metabolism of clopidogrel, prasugrel, esomeprazole, and vonoprazan. Clopidogrel 53-64 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 12-18 30422888-0 2018 Investigating the Effect of Demographics, Clinical Characteristics, and Polymorphism of MDR-1, CYP1A2, CYP3A4, and CYP3A5 on Clopidogrel Resistance. Clopidogrel 125-136 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 103-109 27904973-0 2017 Platelet reactivity and clinical outcomes in patients using CYP3A4-metabolized statins with clopidogrel in percutaneous coronary intervention. Clopidogrel 92-103 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 60-66 27904973-1 2017 Statins are primarily metabolized by cytochrome P450 3A4 (CYP3A4), which reduces clopidogrel to its active metabolite. Clopidogrel 81-92 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 37-56 27904973-1 2017 Statins are primarily metabolized by cytochrome P450 3A4 (CYP3A4), which reduces clopidogrel to its active metabolite. Clopidogrel 81-92 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 58-64 27904973-2 2017 Recent studies suggest that CYP3A4-metabolized statins attenuate clopidogrel"s anti-aggregatory effect on platelets. Clopidogrel 65-76 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 28-34 27904973-10 2017 CYP3A4-metabolized statins slightly inhibit the antiplatelet activity of clopidogrel during dual antiplatelet therapy. Clopidogrel 73-84 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 27350760-2 2016 There has been a concern that statins that are metabolized by cytochrome P450 3A4 may interfere with clopidogrel metabolism at high doses. Clopidogrel 101-112 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 62-81 26891871-0 2017 Impact of CYP3A4*1G Allele on Clinical Pharmacokinetics and Pharmacodynamics of Clopidogrel. Clopidogrel 80-91 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 10-16 26891871-3 2017 The aim of this study was to evaluate the influence of CYP3A4*1G (IVS10+12G>A, rs2242480) on the pharmacokinetics and pharmacodynamics of clopidogrel. Clopidogrel 141-152 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 55-61 26891871-4 2017 METHODS: CYP3A4*1G polymorphism was determined in a group of 82 patients undergoing percutaneous coronary intervention and taking 75 mg of clopidogrel daily. Clopidogrel 139-150 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 9-15 27196064-11 2016 Clopidogrel is therefore now considered to be primarily a CYP3A4/5 substrate. Clopidogrel 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 58-64 27556885-0 2016 Plasma miR-142 accounting for the missing heritability of CYP3A4/5 functionality is associated with pharmacokinetics of clopidogrel. Clopidogrel 120-131 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 58-64 27556885-1 2016 AIM: To investigate whether plasma miRNAs targeting CYP3A4/5 have an impact on the variance of pharmacokinetics of clopidogrel. Clopidogrel 115-126 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 52-58 27556885-3 2016 The association between plasma miRNAs targeting CYP3A4/5 mRNA and clopidogrel pharmacokinetics was analyzed in 31 patients with coronary heart disease who received 300 mg loading dose of clopidogrel. Clopidogrel 66-77 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 48-54 27556885-6 2016 CONCLUSION: miR-142 could account for a part of missing heritability of CYP3A4/5 functionality related to clopidogrel activation. Clopidogrel 106-117 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 72-78 29767595-2 2016 Our results draw attention to the impact of CYP3A4*1B on the clinical effect of clopidogrel during dual antiplatelet therapy after PCI. Clopidogrel 80-91 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 44-50 27133299-0 2016 Associations of CYP3A4, NR1I2, CYP2C19 and P2RY12 polymorphisms with clopidogrel resistance in Chinese patients with ischemic stroke. Clopidogrel 69-80 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 16-22 26329790-3 2015 Clopidogrel and its metabolites inhibit OATP1B1 and CYP3A4 in vitro. Clopidogrel 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 52-58 26767297-2 2015 METHODS: The CES1, cytochrome P450 3A4, CYP450 2C19, CYP450 1A2 and CYP450 2B6 which involved in Clopidogrel metabolism were selected at first, the chemical ligand database were created then, and finally the interaction effects between the ligand database and Clopidogrel metabolism target were explored. Clopidogrel 97-108 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 19-38 26767297-2 2015 METHODS: The CES1, cytochrome P450 3A4, CYP450 2C19, CYP450 1A2 and CYP450 2B6 which involved in Clopidogrel metabolism were selected at first, the chemical ligand database were created then, and finally the interaction effects between the ligand database and Clopidogrel metabolism target were explored. Clopidogrel 260-271 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 19-38 26767297-6 2015 CONCLUSION: It is suggested that Fufang Danshen Dripping Pill has inhibitory effects on Clopidogrel metabolism enzymes target such as CES1, Cytochrome P450 3A4, CYP450 2C19, CYP450 1A2 and CYP450 2B6. Clopidogrel 88-99 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 140-159 25747989-4 2015 Some in vitro studies have suggested that simvastatin could attenuate clopidogrel activation via inhibiting CYP3A activity. Clopidogrel 70-81 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 108-113 25747989-11 2015 In summary, the inhibitory effect of simvastatin on the hydrolysis of clopidogrel and its principal metabolites may have offset the influence of simvastatin-mediated inhibition of CYP3A, and permitted the unaltered formation of the clopidogrel active metabolite. Clopidogrel 70-81 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 180-185 23773422-0 2013 Epidemiology of CYP3A4-mediated clopidogrel drug-drug interactions and their clinical consequences. Clopidogrel 32-43 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 16-22 24719135-2 2014 CYP3A4 is involved in the metabolism of both clopidogrel and dihydropyridine calcium channel blockers (CCBs). Clopidogrel 45-56 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 24986003-9 2014 Previous antiplatelet agent - clopidogrel is ineffective due to genetic polymorphism in P450 (polymorphism of CYP2C19 and CYP3A4 allele - *1 isoforms in function, *2 and *3 non-functioning alleles) and due to failure of metabolic conversion to active molecule. Clopidogrel 30-41 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 122-128 23773422-2 2013 The objective of this study was to evaluate the prevalence and clinical consequences of potential drug-drug interactions of clopidogrel with drugs affecting CYP3A4 activity. Clopidogrel 124-135 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 157-163 23773422-5 2013 RESULTS: In the nationwide analysis, 6.1%, 1.0%, and 20.8% of the clopidogrel-treated patients were exposed to concomitant use of CYP3A4 inhibitors, CYP3A4 inducers, and atorvastatin, respectively. Clopidogrel 66-77 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 130-136 23773422-5 2013 RESULTS: In the nationwide analysis, 6.1%, 1.0%, and 20.8% of the clopidogrel-treated patients were exposed to concomitant use of CYP3A4 inhibitors, CYP3A4 inducers, and atorvastatin, respectively. Clopidogrel 66-77 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 149-155 23773422-12 2013 CYP3A4 inhibitors and atorvastatin may reduce bleedings in clopidogrel users. Clopidogrel 59-70 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 23770199-6 2013 Clopidogrel (10 and 100 muM) was also toxic for HepG2 cells expressing human CYP3A4 (HepG2/CYP3A4) and HepG2 cells co-incubated with CYP3A4 supersomes (HepG2/CYP3A4 supersome), but not for wild-type HepG2 cells (HepG2/wt). Clopidogrel 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 77-83 23770199-6 2013 Clopidogrel (10 and 100 muM) was also toxic for HepG2 cells expressing human CYP3A4 (HepG2/CYP3A4) and HepG2 cells co-incubated with CYP3A4 supersomes (HepG2/CYP3A4 supersome), but not for wild-type HepG2 cells (HepG2/wt). Clopidogrel 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 91-97 23770199-6 2013 Clopidogrel (10 and 100 muM) was also toxic for HepG2 cells expressing human CYP3A4 (HepG2/CYP3A4) and HepG2 cells co-incubated with CYP3A4 supersomes (HepG2/CYP3A4 supersome), but not for wild-type HepG2 cells (HepG2/wt). Clopidogrel 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 91-97 24900388-0 2012 Identification of the Significant Involvement and Mechanistic Role of CYP3A4/5 in Clopidogrel Bioactivation. Clopidogrel 82-93 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 70-76 22651985-8 2012 Pre-incubation with recombinant human CYP3A4 not only caused degradation of clopidogrel and ticlopidine, but also increased cytotoxicity. Clopidogrel 76-87 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 38-44 23770199-6 2013 Clopidogrel (10 and 100 muM) was also toxic for HepG2 cells expressing human CYP3A4 (HepG2/CYP3A4) and HepG2 cells co-incubated with CYP3A4 supersomes (HepG2/CYP3A4 supersome), but not for wild-type HepG2 cells (HepG2/wt). Clopidogrel 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 91-97 23770199-7 2013 Clopidogrel (100 muM) decreased the cellular glutathione content in HepG2/CYP3A4 supersome and triggered an oxidative stress reaction (10 and 100 microM) in HepG2/CYP3A4, but not in HepG2/wt. Clopidogrel 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 74-80 23770199-7 2013 Clopidogrel (100 muM) decreased the cellular glutathione content in HepG2/CYP3A4 supersome and triggered an oxidative stress reaction (10 and 100 microM) in HepG2/CYP3A4, but not in HepG2/wt. Clopidogrel 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 163-169 23770199-8 2013 Glutathione depletion significantly increased the cytotoxicity of clopidogrel (10 and 100 microM) in HepG2/CYP3A4 supersome. Clopidogrel 66-77 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 107-113 23770199-9 2013 Co-incubation with 1 muM ketoconazole or 10mM glutathione almost completely prevented the cytotoxic effect of clopidogrel in HepG2/CYP3A4 and HepG2/CYP3A4 supersome. Clopidogrel 110-121 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 131-137 23770199-9 2013 Co-incubation with 1 muM ketoconazole or 10mM glutathione almost completely prevented the cytotoxic effect of clopidogrel in HepG2/CYP3A4 and HepG2/CYP3A4 supersome. Clopidogrel 110-121 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 148-154 23770199-10 2013 HepG2/CYP3A4 incubated with 100 muM clopidogrel showed mitochondrial damage and cytochrome c release, eventually promoting apoptosis and/or necrosis. Clopidogrel 36-47 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 6-12 23770199-12 2013 In conclusion, clopidogrel incubated with CYP3A4 is associated with the formation of metabolites that are toxic for hepatocytes and can be trapped by glutathione. Clopidogrel 15-26 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 42-48 23770199-13 2013 High CYP3A4 activity and low cellular glutathione stores may be risk factors for clopidogrel-associated hepatocellular toxicity. Clopidogrel 81-92 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 5-11 24023447-3 2013 One of them is clopidogrel drug-drug interaction with CYP2C19 and CYP3A4 enzyme inhibitors. Clopidogrel 15-26 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 66-72 24023447-10 2013 The use of the potential CYP3A4 inhibitors - lipophilic statins and CCB - was increased after the prescription of clopidogrel too. Clopidogrel 114-125 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 25-31 24023447-12 2013 CONCLUSION: In the primary health care practices, it is revealed that there is co-medication of clopidogrel with weak CYP3A4 inhibitors, such as lipophilic statins and amlodipine, and with the moderate CYP2C19 inhibitor - omeprazole. Clopidogrel 96-107 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 118-124 23400261-0 2013 CYP3A4 genetic status may be associated with increased vulnerability to the inhibitory effect of calcium-channel blockers on clopidogrel. Clopidogrel 125-136 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 23400261-1 2013 BACKGROUND: Calcium-channel blockers (CCBs) inhibit the CYP3A4 enzyme, which is involved in clopidogrel activation. Clopidogrel 92-103 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 56-62 23400261-3 2013 We investigated the relationship between CYP3A4 genotype and the inhibitory effect of CCBs on clopidogrel response. Clopidogrel 94-105 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 41-47 23400261-11 2013 The number of CYP3A4 (IVS10+12G>A) A-alleles may be associated with an increased vulnerability to the effects of CCBs on clopidogrel response variation. Clopidogrel 124-135 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 14-20 24900388-7 2012 Identifying the significant involvement of CYP3A4/5 and characterizing its mechanistic role in clopidogrel bioactivation might assist future pharmacogenomic studies in exploring the full mechanism underlying clopidogrel efficacy. Clopidogrel 208-219 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 43-49 22243420-1 2012 WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The CYP3A4 inhibition by lipophilic statins may attenuate the effectiveness of clopidogrel. Clopidogrel 123-134 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 48-54 22428615-11 2012 Moreover, incubation with inhibitors of CYP3A, CYP2B6 and CYP2C19 significantly reduced clopidogrel bioactivation while a PON1 inhibitor, EDTA, had only a weak inhibitory effect. Clopidogrel 88-99 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 40-45 22428615-13 2012 Moreover, CYP2C19, CYP2B6 and CYP3A play important roles in the bioactivation of clopidogrel. Clopidogrel 81-92 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 30-35 22507978-1 2012 AIMS: CYP3A4-metabolized statins can influence the pharmacodynamic effect of clopidogrel. Clopidogrel 77-88 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 6-12 22507978-12 2012 CONCLUSIONS: Among PCI-treated patients with HPR during co-administration of clopidogrel and atorvastatin, switching to a non-CYP3A4-metabolized statin can significantly decrease platelet reactivity and the prevalence of HPR. Clopidogrel 77-88 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 126-132 22735685-2 2012 Amlodipine is a well-known inhibitor of CYP 3A4, an isoenzyme of CYP3A that activates clopidogrel. Clopidogrel 86-97 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 40-47 22735685-4 2012 In the presence of CYP3A4 inhibitors such as amlodipine, the genetic variation of CYP3A5, the isoenzyme responsible for the backup CYP3A activity, may play an important role in clopidogrel activation. Clopidogrel 177-188 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 19-25 19337788-0 2009 Frequency of CYP3A4, CYP3A5, CYP2C9, and CYP2C19 variant alleles in patients receiving clopidogrel that experience repeat acute coronary syndrome. Clopidogrel 87-98 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 13-19 21828263-6 2011 These studies show that, in vitro, CYP3A4/5, 2C19, and 2B6 are individually capable of converting clopidogrel and prasugrel to the AM and that the cytochrome P450 preference for these two thienopyridines is very similar. Clopidogrel 98-109 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 35-49 21826477-6 2011 Several other drugs (metabolized through CYP3A4 such as statins or antifungals) similarly impact the pharmacologic response to clopidogrel. Clopidogrel 127-138 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 41-47 21568918-4 2011 PPIs might diminish the antiplatelet effects and the clinical effectiveness of clopidogrel possibly through inhibition of CYP2C19 and CYP3A4 isoenzymes. Clopidogrel 79-90 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 134-140 20980920-0 2011 The effect of St John"s Wort on the pharmacodynamic response of clopidogrel in hyporesponsive volunteers and patients: increased platelet inhibition by enhancement of CYP3A4 metabolic activity. Clopidogrel 64-75 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 167-173 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. Clopidogrel 200-211 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. Clopidogrel 200-211 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 134-139 21073556-11 2010 For the clopidogrel CYP2C19 and CYP3A4/5 interactions, there is good evidence that these interactions occur. Clopidogrel 8-19 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 32-38 20942779-10 2010 Several studies have also demonstrated that CYP3A4/5 and CYP1A2 are important in clopidogrel bioactivation and should also be considered as potential targets for unwanted drug-drug interactions. Clopidogrel 81-92 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 44-50 20664903-2 2010 Drug-drug interaction between statins metabolised by cytochrome P450 3A4 and clopidogrel have been claimed to attenuate the inhibitory effect of clopidogrel. Clopidogrel 145-156 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-72 19636246-5 2010 Polymorphisms in the hepatic enzymes involved in the metabolism of clopidogrel (e.g., CYP 1A2, CYP3A4, CYP2C19) or within the platelet membrane receptor (P2Y12) and/or polymorphism of platelet integrin alphaIIbbeta3 or integrin alpha2beta1 may affect platelet responses and could influence response to clopidogrel administration. Clopidogrel 67-78 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 95-101 19812348-10 2010 These studies showed that CYP2C19 contributed substantially to both oxidative steps required in the formation of clopidogrel active metabolite and that CYP3A4 contributed substantially to the second oxidative step. Clopidogrel 113-124 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 152-158 19531897-1 2009 BACKGROUND: The P2Y(12) adenosine diphosphate (ADP) receptor blocker, clopidogrel, an essential drug for the prevention of stent thrombosis after percutaneous coronary intervention (PCI), is a prodrug that requires CYP2C19- and CYP3A4-mediating activation. Clopidogrel 70-81 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 228-234 19531897-4 2009 The effect of polymorphisms of CYP2C19, CYP3A4 and P2Y(12) on the antiplatelet effect of clopidogrel in clinical patients was examined in the present study. Clopidogrel 89-100 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 40-46 22313038-0 2012 Different effects of proton pump inhibitors and famotidine on the clopidogrel metabolic activation by recombinant CYP2B6, CYP2C19 and CYP3A4. Clopidogrel 66-77 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 134-140 22313038-1 2012 Inhibitory potential of proton pump inhibitors (PPIs) and famotidine, an H(2) receptor antagonist, on the metabolic activation of clopidogrel was evaluated using recombinant CYP2B6, CYP2C19 and CYP3A4. Clopidogrel 130-141 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 194-200 21834799-1 2012 BACKGROUND: The CYP3A4 inhibition by calcium channel blockers (CCBs) may attenuate the effectiveness of clopidogrel. Clopidogrel 104-115 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 16-22 22613391-3 2012 A total of 1021 patients were enrolled, with 178 of them prescribed clopidogrel and 843 patients were administrated clopidogrel combined with statins (CYP3A4-metabolized statins 636 and non CYP3A4-metabolized statins 207). Clopidogrel 116-127 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 151-157 22319066-2 2012 BACKGROUND: Clopidogrel is an inactive prodrug; it is converted to its active metabolite through the cytochrome P450 (CYP3A4) pathway, which also metabolizes calcium channel blockers (CCBs). Clopidogrel 12-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 118-124 20735423-4 2010 KEY RESULTS: Experiments using HLM or specific CYPs (3A4, 2C19) revealed that at clopidogrel concentrations >10 microM, CYP3A4 was primarily responsible for clopidogrel biotransformation. Clopidogrel 81-92 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 123-129 20735423-4 2010 KEY RESULTS: Experiments using HLM or specific CYPs (3A4, 2C19) revealed that at clopidogrel concentrations >10 microM, CYP3A4 was primarily responsible for clopidogrel biotransformation. Clopidogrel 160-171 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 123-129 20735423-6 2010 Clarithromycin, another CYP3A4 inhibitor, impaired clopidogrel biotransformation and antiplatelet activity almost as effectively as ketoconazole. Clopidogrel 51-62 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 24-30 20735423-7 2010 The CYP3A4 substrates atorvastatin and simvastatin both inhibited clopidogrel biotransformation and antiplatelet activity, less potently than ketoconazole. Clopidogrel 66-77 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 4-10 20735423-11 2010 CONCLUSIONS AND IMPLICATIONS: At clopidogrel concentrations >10 microM, CYP3A4 is mainly responsible for clopidogrel biotransformation, whereas CYP2C19 contributes only at clopidogrel concentrations < or =10 microM. Clopidogrel 33-44 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 75-81 20735423-11 2010 CONCLUSIONS AND IMPLICATIONS: At clopidogrel concentrations >10 microM, CYP3A4 is mainly responsible for clopidogrel biotransformation, whereas CYP2C19 contributes only at clopidogrel concentrations < or =10 microM. Clopidogrel 108-119 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 75-81 20735423-11 2010 CONCLUSIONS AND IMPLICATIONS: At clopidogrel concentrations >10 microM, CYP3A4 is mainly responsible for clopidogrel biotransformation, whereas CYP2C19 contributes only at clopidogrel concentrations < or =10 microM. Clopidogrel 108-119 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 75-81 19246723-8 2009 However, the major oxidative metabolic pathway for clopidogrel by which the reactive intermediate is formed is CYP3A4. Clopidogrel 51-62 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 111-117 19253920-2 2009 Previous studies have suggested that some statins may inhibit the antiplatelet effects of clopidogrel via competitive metabolism of its activating enzyme cytochrome P450 3A4 (CYP3A4). Clopidogrel 90-101 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 154-173 19253920-2 2009 Previous studies have suggested that some statins may inhibit the antiplatelet effects of clopidogrel via competitive metabolism of its activating enzyme cytochrome P450 3A4 (CYP3A4). Clopidogrel 90-101 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 175-181 19253920-11 2009 CONCLUSIONS: In this PCI cohort, the association of clopidogrel with CYP3A4-metabolized statins did not demonstrate an increased early risk of adverse cardiovascular events, although a small risk could not be completely excluded. Clopidogrel 52-63 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 69-75 19337788-2 2009 This research evaluated the frequency of variant alleles in the genes coding for CYP3A4, CYP3A5, CYP2C9, and CYP2C19 enzymes in patients on clopidogrel therapy and experiencing repeat acute coronary syndrome (ACS) compared to a control group with a matching ethnic composition. Clopidogrel 140-151 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 81-87 19007592-1 2008 OBJECTIVES: Because of the known CYP3A4 inhibition by calcium-channel blockers (CCBs), we hypothesized that there might be a drug-drug interaction between clopidogrel and dihydropyridines in patients with coronary artery disease. Clopidogrel 155-166 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 33-39 19067731-8 2009 Heterogeneity in the way patients respond to aspirin and clopidogrel may in part reflect variation in cyclooxygenase (COX)-1, COX-2, glycoprotein (GP) Ib alpha, GP Ia/IIa, GP IIb/IIIa, UGT1A6*2, P2Y(1), P2Y(12), CYP2C9, CYP3A4 and CYP3A5 genotypes. Clopidogrel 57-68 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 220-226 19007592-2 2008 BACKGROUND: Clopidogrel is activated by CYP3A4, which also metabolizes CCBs of the dihydropyridine class. Clopidogrel 12-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 40-46 18474675-2 2008 Mechanism-based CYP2B6 inhibitors (i.e., clopidogrel, ticlopidine, and triethylenethiophoramide) significantly inhibited the formation of M1 from sibutramine and M2 from M1, respectively; in contrast, no effect was observed when using potent inhibitors of eight P450 isozymes (CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A). Clopidogrel 41-52 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 338-343 19544679-3 2008 Recent studies suggest that statins metabolized by CYP3A4 attenuate the anti-aggregatory effect of clopidogrel. Clopidogrel 99-110 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 51-57 18440347-1 2008 BACKGROUND: Clopidogrel is inactive in vitro and is metabolized by hepatic cytochrome P-450-3A4 to produce active metabolites. Clopidogrel 12-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 75-95 18385991-1 2008 OBJECTIVE: Clopidogrel is activated by cytochrome P450 3A (CYP3A) to generate an active metabolite that inhibits adenosine diphosphate (ADP)-induced platelet aggregation through irreversible binding to the platelet P2Y12 receptor. Clopidogrel 11-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 39-57 18385991-1 2008 OBJECTIVE: Clopidogrel is activated by cytochrome P450 3A (CYP3A) to generate an active metabolite that inhibits adenosine diphosphate (ADP)-induced platelet aggregation through irreversible binding to the platelet P2Y12 receptor. Clopidogrel 11-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 59-64 17697139-0 2007 Influence of CYP2C19 and CYP3A4 gene polymorphisms on clopidogrel responsiveness in healthy subjects. Clopidogrel 54-65 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 25-31 18004210-1 2007 OBJECTIVES: The aim of this study was to evaluate the effect of polymorphisms affecting the clopidogrel metabolism (CYP3A4 IVS10+12G/A and CYP2C19*2) and the P2Y12 receptor (P2Y12 T744C) on modulating platelet function in acute coronary syndrome patients on dual antiplatelet treatment. Clopidogrel 92-103 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 116-122 17261397-2 2007 Previous laboratory studies have shown a possible drug-drug interaction of statins metabolized by cytochrome P450 3A4 and clopidogrel (prodrug metabolized by cytochrome P450 3A4), resulting in an impaired inhibitory effect of clopidogrel on platelet aggregation. Clopidogrel 122-133 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 158-177 17659194-2 2007 BACKGROUND: There are conflicting data regarding whether statins predominantly metabolized by CYP3A4 reduce the metabolism of clopidogrel to its active metabolite and diminish its clinical efficacy. Clopidogrel 126-137 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 94-100 17361128-3 2007 Clopidogrel"s activation involves two sequential steps by CYP3A, CYP1A2, CYP2C9, CYP2C19, and/or CYP2B6. Clopidogrel 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 58-63 17361128-9 2007 We conclude that CYP3A4 and CYP3A5 inhibition by ketoconazole affects formation of clopidogrel"s but not prasugrel"s active metabolite. Clopidogrel 83-94 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 17-23 17261397-2 2007 Previous laboratory studies have shown a possible drug-drug interaction of statins metabolized by cytochrome P450 3A4 and clopidogrel (prodrug metabolized by cytochrome P450 3A4), resulting in an impaired inhibitory effect of clopidogrel on platelet aggregation. Clopidogrel 226-237 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 98-117 17261397-2 2007 Previous laboratory studies have shown a possible drug-drug interaction of statins metabolized by cytochrome P450 3A4 and clopidogrel (prodrug metabolized by cytochrome P450 3A4), resulting in an impaired inhibitory effect of clopidogrel on platelet aggregation. Clopidogrel 226-237 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 158-177 16875906-2 2006 A concern has been raised that atorvastatin may competitively inhibit the metabolism of the prodrug clopidogrel to its active metabolites by the cytochrome P450 3A4 (CYP3A4) enzyme, thereby potentially negating its antiplatelet effect. Clopidogrel 100-111 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 145-164 17008981-6 2006 Clopidogrel is metabolized to an active thiol metabolite by the CYP 3A4 enzyme. Clopidogrel 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 64-71 17008981-7 2006 Some HMG CoA reductase inhibitors have the ability to inhibit the CYP 3A4 enzyme, which can result in a possible interaction if administered concomitantly with clopidogrel. Clopidogrel 160-171 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 66-73 16875906-2 2006 A concern has been raised that atorvastatin may competitively inhibit the metabolism of the prodrug clopidogrel to its active metabolites by the cytochrome P450 3A4 (CYP3A4) enzyme, thereby potentially negating its antiplatelet effect. Clopidogrel 100-111 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 166-172 16645157-0 2006 Contribution of gene sequence variations of the hepatic cytochrome P450 3A4 enzyme to variability in individual responsiveness to clopidogrel. Clopidogrel 130-141 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 56-75 16645157-1 2006 OBJECTIVE: Metabolic activity of cytochrome P450 (CYP) 3A4 has been associated with clopidogrel response variability. Clopidogrel 84-95 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 33-58 16645157-2 2006 Because metabolic activity of CYP3A4 is genetically regulated, we hypothesized that genetic variations of this enzyme may contribute to clopidogrel response variability. Clopidogrel 136-147 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 30-36 16645157-10 2006 CONCLUSIONS: The IVS10+12G>A polymorphism of the CYP3A4 gene modulates platelet activation in patients treated with clopidogrel and may therefore contribute to clopidogrel response variability. Clopidogrel 119-130 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 52-58 16645157-10 2006 CONCLUSIONS: The IVS10+12G>A polymorphism of the CYP3A4 gene modulates platelet activation in patients treated with clopidogrel and may therefore contribute to clopidogrel response variability. Clopidogrel 163-174 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 52-58 16754899-1 2006 BACKGROUND: Clopidogrel is a prodrug requiring metabolism by cytochrome P450 3A (CYP3A) isoenzymes, including CYP3A5, in order to be active. Clopidogrel 12-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 61-79 16754899-1 2006 BACKGROUND: Clopidogrel is a prodrug requiring metabolism by cytochrome P450 3A (CYP3A) isoenzymes, including CYP3A5, in order to be active. Clopidogrel 12-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 81-86 16754899-10 2006 INTERPRETATION: People with the CYP3A5 non-expressor genotype are vulnerable to drug interactions between clopidogrel and CYP3A inhibitors. Clopidogrel 106-117 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 32-37 15679472-2 2005 Clopidogrel is an inactive prodrug, which requires activation by the cytochrome P450 3A4 system in order to exert its antiplatelet action. Clopidogrel 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 69-88 16264203-1 2005 BACKGROUND: A recent ex vivo study suggests that the metabolic activation of clopidogrel is catalyzed by cytochrom P450 (CYP) 3A4 and is competitively inhibited by atorvastatin, but not pravastatin. Clopidogrel 77-88 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 115-129 16113837-1 2005 Recent studies suggest that cytochrome P450 (CYP) 3A4 metabolized statins attenuate the antiaggregatory effect of clopidogrel. Clopidogrel 114-125 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 28-53 16503718-3 2006 Investigators have proposed that the use of statins that are metabolized by the cytochrome P450 (CYP) system may diminish the conversion of clopidogrel to its active form by inhibiting the CYP3A4 isoenzyme. Clopidogrel 140-151 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 189-195 16611111-3 2006 The assumption exists that the effect of clopidogrel in inhibiting platelet aggregation is attenuated by co-administration of lipophilic statins such as atorvastatin or simvastatin which are metabolised by the CYP3A4 system to inactive substrates. Clopidogrel 41-52 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 210-216 16611111-8 2006 However, these clinical studies showed a trend towards a diminishing effect of clopidogrel on those treated with cytochrome CYP3A4 metabolised statins. Clopidogrel 79-90 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 124-130 16611111-11 2006 This effect of clopidogrel resistance seems to be more important as the potential interference between CYP3A4 metabolized statins and clopidogrel. Clopidogrel 15-26 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 103-109 15679472-4 2005 From a theoretical point of view, a clinical relevant interaction may exist between clopidogrel and cytochrome P450 3A4 metabolized statins. Clopidogrel 84-95 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 100-119 15604326-1 2005 OBJECTIVE: To assess a clinically significant interaction between cytochrome P450 3A4 (CYP3A4) metabolised statin and clopidogrel. Clopidogrel 118-129 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 66-85 15604326-1 2005 OBJECTIVE: To assess a clinically significant interaction between cytochrome P450 3A4 (CYP3A4) metabolised statin and clopidogrel. Clopidogrel 118-129 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 87-93 15604326-6 2005 MAIN OUTCOME MEASURE: Association of CYP3A4 metabolised statin and clopidogrel use with in-hospital and six month mortality. Clopidogrel 67-78 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 37-43 15604326-9 2005 CONCLUSIONS: Use of a combination of a CYP3A4 statin plus clopidogrel was associated with lower six month mortality and morbidity in patients with acute coronary syndromes. Clopidogrel 58-69 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 39-45 12515739-2 2003 Because atorvastatin is metabolized by cytochrome P450 (CYP) 3A4, we hypothesized that clopidogrel might be activated by CYP3A4. Clopidogrel 87-98 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 121-127 12515739-7 2003 CONCLUSIONS: CYP3A4 activates clopidogrel. Clopidogrel 30-41 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 13-19 14707025-0 2004 Contribution of hepatic cytochrome P450 3A4 metabolic activity to the phenomenon of clopidogrel resistance. Clopidogrel 84-95 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 24-43 14707025-3 2004 Because the prodrug clopidogrel is activated by hepatic cytochrome P450 (CYP) 3A4, we hypothesized that interindividual variability in clopidogrel efficacy might be related to interindividual differences in CYP3A4 metabolic activity. Clopidogrel 20-31 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 56-81 14707025-3 2004 Because the prodrug clopidogrel is activated by hepatic cytochrome P450 (CYP) 3A4, we hypothesized that interindividual variability in clopidogrel efficacy might be related to interindividual differences in CYP3A4 metabolic activity. Clopidogrel 20-31 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 207-213 14707025-3 2004 Because the prodrug clopidogrel is activated by hepatic cytochrome P450 (CYP) 3A4, we hypothesized that interindividual variability in clopidogrel efficacy might be related to interindividual differences in CYP3A4 metabolic activity. Clopidogrel 135-146 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 56-81 14707025-3 2004 Because the prodrug clopidogrel is activated by hepatic cytochrome P450 (CYP) 3A4, we hypothesized that interindividual variability in clopidogrel efficacy might be related to interindividual differences in CYP3A4 metabolic activity. Clopidogrel 135-146 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 207-213 14707025-10 2004 Percent platelet aggregation after clopidogrel inversely correlated with CYP3A4 activity (r=-0.6, P=0.003). Clopidogrel 35-46 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 73-79 14707025-12 2004 CONCLUSIONS: Clopidogrel administration results in interindividual variability in platelet inhibition, which correlates with CYP3A4 metabolic activity. Clopidogrel 13-24 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 125-131 14522569-9 2003 CONCLUSION: Certain statins which are substrates of the CYP3A4 isoform competitively inhibit the metabolic activation of clopidogrel. Clopidogrel 121-132 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 56-62 12925453-1 2003 BACKGROUND: Statins primarily metabolized by cytochrome P450 3A4 (CYP3A4) reportedly reduce clopidogrel"s metabolism to active metabolite, thus attenuating its inhibition of platelet aggregation ex vivo. Clopidogrel 92-103 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 45-64 12925453-1 2003 BACKGROUND: Statins primarily metabolized by cytochrome P450 3A4 (CYP3A4) reportedly reduce clopidogrel"s metabolism to active metabolite, thus attenuating its inhibition of platelet aggregation ex vivo. Clopidogrel 92-103 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 66-72 12925453-9 2003 This clopidogrel benefit was similar with statin use, irrespective of treatment with a CYP3A4-MET (7.6% clopidogrel, 11.8% control, RRR 36.4%, 95% CI 3.9 to 57.9; P=0.03) or non-CYP3A4-MET statin (5.4% clopidogrel, 13.6% control, RRR 60.6%, 95% CI -23.9 to 87.4; P=0.11). Clopidogrel 5-16 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 178-184 12925453-12 2003 CONCLUSIONS: Although ex vivo testing has suggested a potential negative interaction when coadministering a CYP3A4-metabolized statin with clopidogrel, this was not clinically observed statistically in a post hoc analysis of a placebo-controlled study. Clopidogrel 139-150 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 108-114 12485953-2 2003 Clopidogrel is frequently administered to patients in conjunction with the CYP3A4 substrate atorvastatin (Lipitor). Clopidogrel 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 75-81 12485953-3 2003 Since clinical studies indicate that atorvastatin inhibits the antiplatelet activity of clopidogrel, we investigated whether CYP3A4 metabolized clopidogrel in vitro. Clopidogrel 144-155 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 125-131 12485953-6 2003 CYP3A4 and 3A5 metabolized clopidogrel at a significantly higher rate than eight other p450 isozymes, suggesting that CYP3A4 and 3A5 are primarily responsible for in vivo clopidogrel metabolism. Clopidogrel 27-38 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 12485953-6 2003 CYP3A4 and 3A5 metabolized clopidogrel at a significantly higher rate than eight other p450 isozymes, suggesting that CYP3A4 and 3A5 are primarily responsible for in vivo clopidogrel metabolism. Clopidogrel 27-38 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 118-124 12485953-6 2003 CYP3A4 and 3A5 metabolized clopidogrel at a significantly higher rate than eight other p450 isozymes, suggesting that CYP3A4 and 3A5 are primarily responsible for in vivo clopidogrel metabolism. Clopidogrel 171-182 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 12485953-6 2003 CYP3A4 and 3A5 metabolized clopidogrel at a significantly higher rate than eight other p450 isozymes, suggesting that CYP3A4 and 3A5 are primarily responsible for in vivo clopidogrel metabolism. Clopidogrel 171-182 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 118-124 12485953-7 2003 Clopidogrel interacts with human CYP3A4 with a spectral dissociation constant (K(s)), K(m), and V(max) of 12 microM, 14 +/- 1 microM and 6.7 +/- 1 nmol min(-1) nmol p450(-1), respectively. Clopidogrel 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 33-39 12485953-10 2003 Since CYP3A4 and 3A5 metabolize clopidogrel faster than other human p450 isozymes and are the most abundant p450s in human liver, they are predicted to be predominantly responsible for the activation of clopidogrel in vivo. Clopidogrel 32-43 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 6-12 12485953-10 2003 Since CYP3A4 and 3A5 metabolize clopidogrel faster than other human p450 isozymes and are the most abundant p450s in human liver, they are predicted to be predominantly responsible for the activation of clopidogrel in vivo. Clopidogrel 203-214 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 6-12