PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 29255993-5 2018 Given their lipophilicity and CYP3A4 metabolic pathway, atorvastatin and simvastatin presented a higher prevalence of drug-drug interactions while fluvastatin presented the lowest prevalence. Simvastatin 73-84 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 30-36 30808332-6 2019 CONCLUSION: Simvastatin, as well as lovastatin, because of their CYP3A4 metabolism, and to a lesser extent atorvastatin, which is only partially metabolized by CYP3A4, are the HMG-CoA reductase inhibitors with the greatest risk of drug interactions and should not be used in patients under HIV-therapy. Simvastatin 12-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 65-71 29255993-7 2018 The second most frequent contraindicated drug-drug interaction involved CYP3A4 interaction between atorvastatin or simvastatin with either posaconazole or erythromycin. Simvastatin 115-126 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 72-78 27722854-3 2017 This study evaluated the pharmacokinetic profile of simvastatin (a CYP3A4 substrate) before and 1 week after a single dose of sarilumab (a human monoclonal antibody [mAb] blocking the IL-6Ralpha) in patients with RA, to assess potential interaction. Simvastatin 52-63 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 67-73 29063606-5 2018 Although CP studies are limited, meta-analysis-based reduction in CYP1A2, CYP2C19, and CYP3A4 enzyme abundances in a virtual oncology population effectively captures CP-PK for caffeine, theophylline, midazolam, simvastatin, omeprazole, and a subset of oncology compounds. Simvastatin 211-222 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 87-93 29167415-2 2017 Yet combined therapeutic regimens have the potential of pharmacological interaction with both ticagrelor and simvastatin being metabolized by CYP3A4. Simvastatin 109-120 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 142-148 27605198-5 2016 Three commonly used statins-simvastatin, atorvastatin and lovastatin-are metabolised by the liver enzyme CYP3A4. Simvastatin 28-39 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 105-111 28350522-0 2017 The influences of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of simvastatin, in relation to CYP3A4 inhibition. Simvastatin 73-84 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 101-107 28350522-1 2017 AIM: To investigate the combined effects of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of simvastatin and its active metabolite simvastatin acid, in relation to CYP3A4 inhibition. Simvastatin 99-110 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 170-176 28350522-7 2017 SLCO1B1 genotyping may be particularly beneficial in simvastatin users who are co-administered CYP3A4 inhibitors. Simvastatin 53-64 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 95-101 26502771-11 2016 Simvastatin inhibits the CYP3A4 isoenzyme. Simvastatin 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 25-31 26765458-1 2016 Some statins (simvastatin, lovastatin, and atorvastatin) are metabolized by cytochrome P450s 3A4 (CYP3A4). Simvastatin 14-25 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 76-96 26765458-1 2016 Some statins (simvastatin, lovastatin, and atorvastatin) are metabolized by cytochrome P450s 3A4 (CYP3A4). Simvastatin 14-25 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 98-104 26164721-0 2015 Individual and Combined Associations of Genetic Variants in CYP3A4, CYP3A5, and SLCO1B1 With Simvastatin and Simvastatin Acid Plasma Concentrations. Simvastatin 93-104 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 60-66 24927617-9 2014 The interaction is due to inhibition of CYP3A4-mediated simvastatin clearance. Simvastatin 56-67 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 40-46 25274942-3 2015 We analyzed the association of CYP3A4*22 allele with response to atorvastatin and simvastatin. Simvastatin 82-93 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 31-37 25274942-7 2015 RESULTS: In the entire cohort population, 41 individuals carried CYP3A4*22 allele (18 in atorvastatin and 23 in simvastatin treatment). Simvastatin 112-123 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 65-71 25324279-7 2015 The closest prediction was obtained for CYP3A (simvastatin) DDI when the competitive inhibition from both AMIO and MDEA was considered, for CYP2D6 (dextromethorphan) DDI when the competitive inhibition from AMIO and the competitive plus time-dependent inhibition from MDEA were incorporated, and for CYP2C9 (warfarin) DDI when the competitive plus time-dependent inhibition from AMIO and the competitive inhibition from MDEA were considered. Simvastatin 47-58 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 40-45 25747989-4 2015 Some in vitro studies have suggested that simvastatin could attenuate clopidogrel activation via inhibiting CYP3A activity. Simvastatin 42-53 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. Simvastatin 37-48 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 180-185 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. Simvastatin 145-156 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 180-185 25932626-1 2015 BACKGROUND: The concomitant use of cytochrome P450 3A4 (CYP3A4) metabolized statins (simvastatin, lovastatin, and atorvastatin) with CYP3A4 inhibitors has been shown to increase the rate of adverse events. Simvastatin 85-96 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 35-54 25932626-1 2015 BACKGROUND: The concomitant use of cytochrome P450 3A4 (CYP3A4) metabolized statins (simvastatin, lovastatin, and atorvastatin) with CYP3A4 inhibitors has been shown to increase the rate of adverse events. Simvastatin 85-96 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 56-62 25932626-1 2015 BACKGROUND: The concomitant use of cytochrome P450 3A4 (CYP3A4) metabolized statins (simvastatin, lovastatin, and atorvastatin) with CYP3A4 inhibitors has been shown to increase the rate of adverse events. Simvastatin 85-96 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 133-139 26736984-1 2015 BACKGROUND: Concomitant use of simvastatin, a HMG-CoA reductase inhibitor, with a potent CYP3A4 inhibitor, itraconazole, can result in a serious drug-drug interaction induced severe adverse event, rhabdomyolysis. Simvastatin 31-42 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 89-95 25051018-0 2014 CYP3A4*22 and CYP3A5*3 are associated with increased levels of plasma simvastatin concentrations in the cholesterol and pharmacogenetics study cohort. Simvastatin 70-81 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 25051018-1 2014 OBJECTIVE: Simvastatin is primarily metabolized by CYP3A4. Simvastatin 11-22 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 51-57 25051018-3 2014 We aim to determine whether CYP3A4*22 and CYP3A5*3 alleles are associated with increased plasma concentrations of simvastatin lactone (SV) and simvastatin acid (SVA). Simvastatin 114-133 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 28-34 25051018-4 2014 This is the first report evaluating associations between in-vivo simvastatin concentrations and CYP3A4*22, alone or in a combined CYP3A4/5 genotype-defined classification. Simvastatin 65-76 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 96-102 25051018-7 2014 Associations between simvastatin concentrations and CYP3A4*22 and CYP3A5*3 alleles were tested separately and in a combined CYP3A4/5 genotype-defined classification system. Simvastatin 21-32 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 52-58 25051018-13 2014 CONCLUSION: Genetic variation in CYP3A4 was associated with plasma simvastatin concentrations in self-reported Whites. Simvastatin 67-78 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 33-39 25051018-14 2014 Genetic variations in CYP3A4 and CYP3A5 were associated with plasma simvastatin concentrations in self-reported African-Americans. Simvastatin 68-79 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 22-28 25041770-1 2014 Clarithromycin is the most documented cytochrome P450 3A4 (CYP3A4) inhibitor to cause an adverse interaction with simvastatin. Simvastatin 114-125 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 38-57 25041770-1 2014 Clarithromycin is the most documented cytochrome P450 3A4 (CYP3A4) inhibitor to cause an adverse interaction with simvastatin. Simvastatin 114-125 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 59-65 24430948-2 2014 The polymorphic enzyme P450 oxidoreductase (POR) transfers electrons from nicotinamide adenine dinucleotide phosphate (NADPH) to cytochrome P450 (CYP) 3A enzymes, which metabolize atorvastatin and simvastatin. Simvastatin 197-208 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 129-153 24865757-5 2014 Lomitapide undergoes hepatic metabolism via cytochrome P-450 (CYP) isoenzyme 3A4 and interacts with CYP3A4 substrates including atorvastatin and simvastatin; dose adjustment is recommended when lomitapide is used concurrently with these agents. Simvastatin 145-156 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 100-106 24974574-4 2014 Simvastatin, atorvastatin and lovastatin are metabolized by CYP3A4, fluvastatin by CYP2C9, while rosuvastatin by CYP2C9 and 2C19. Simvastatin 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 60-66 23939663-0 2013 Reduced exposure variability of the CYP3A substrate simvastatin by dose individualization to CYP3A activity. Simvastatin 52-63 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 36-41 25571290-1 2014 BACKGROUND: Simvastatin is a HMG-CoA reductase Inhibitor and a substrate of CYP3A4. Simvastatin 12-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 76-82 25571292-4 2014 Simvastatin, a commonly used HMG-CoA reductase inhibitor for the treatment of hypercholesterolemia is extensively metabolized by CYP3A4. Simvastatin 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 129-135 25571293-1 2014 BACKGROUND: Simvastatin, a commonly used HMG-CoA reductase inhibitor, is extensively metabolized by CYP3A4. Simvastatin 12-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 100-106 25571293-2 2014 Therefore, co-administration of simvastatin and CYP3A4 inhibitor can affect simvastatin pharmacokinetics. Simvastatin 76-87 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 48-54 23965645-5 2014 When CYP3A4/5 polymorphisms were assessed by a mixture model, extensive metabolizers yielded a decrease in simvastatin bioavailability of 81% and a decrease in simvastatin clearance by 4.6 times as compared to poor metabolizers. Simvastatin 107-118 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 5-11 23965645-5 2014 When CYP3A4/5 polymorphisms were assessed by a mixture model, extensive metabolizers yielded a decrease in simvastatin bioavailability of 81% and a decrease in simvastatin clearance by 4.6 times as compared to poor metabolizers. Simvastatin 160-171 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 5-11 24379677-11 2014 The interaction with simvastatin seems mainly driven by CYP3A4 inhibition at the intestinal level, whereas the interaction with atorvastatin is more due to hepatic CYP3A4 inhibition. Simvastatin 21-32 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 56-62 24379677-12 2014 The interaction of CYP3A4 inhibitor with simvastatin has been more pronounced compared with atorvastatin. Simvastatin 41-52 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 19-25 24256019-12 2013 Therefore, statins metabolized through CYP3A4 (simvastatin, lovastatin and atorvastatin) are the ones with the highest number of clinically relevant interactions. Simvastatin 47-58 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 39-45 23939663-0 2013 Reduced exposure variability of the CYP3A substrate simvastatin by dose individualization to CYP3A activity. Simvastatin 52-63 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 93-98 23939663-1 2013 This study aimed to demonstrate that the dose of a CYP3A substrate (simvastatin) can be adapted individually on the basis of CYP3A activity as assessed by midazolam metabolic clearance. Simvastatin 68-79 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 51-56 23939663-1 2013 This study aimed to demonstrate that the dose of a CYP3A substrate (simvastatin) can be adapted individually on the basis of CYP3A activity as assessed by midazolam metabolic clearance. Simvastatin 68-79 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 125-130 23939663-7 2013 CYP3A activity-based dose adaptation can be used to reduce interindividual variability in simvastatin exposure. Simvastatin 90-101 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-5 23732466-0 2013 CYP3A4-catalyzed simvastatin metabolism as a non-invasive marker of small intestinal health in celiac disease. Simvastatin 17-28 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 23703578-6 2013 Drug-drug interactions are dependent on statins" pharmacokinetic profile: simvastatin, lovastatin and atorvastatin are metabolized through cytochrome P450 (CYP) 3A, while the metabolism of the other statins is independent of this CYP. Simvastatin 74-85 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 139-163 23703578-14 2013 Simvastatin and lovastatin metabolized through CYP3A have the highest potency for drug-drug interaction with potent CYP3A inhibitors such as ritonavir- or cobicistat-boosted HIV-PI or the hepatitis C virus (HCV) PI, telaprevir or boceprevir, and therefore their coadministration is contraindicated. Simvastatin 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 47-52 23703578-14 2013 Simvastatin and lovastatin metabolized through CYP3A have the highest potency for drug-drug interaction with potent CYP3A inhibitors such as ritonavir- or cobicistat-boosted HIV-PI or the hepatitis C virus (HCV) PI, telaprevir or boceprevir, and therefore their coadministration is contraindicated. Simvastatin 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 116-121 23334403-0 2013 Almorexant effects on CYP3A4 activity studied by its simultaneous and time-separated administration with simvastatin and atorvastatin. Simvastatin 105-116 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 22-28 23930676-7 2013 CONCLUSION: The minor alleles of the PPARA rs4253728 and rs4823613 polymorphisms are associated with a better total and LDL-cholesterol-lowering response to simvastatin, possibly through influence on CYP3A4. Simvastatin 157-168 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 200-206 23334403-10 2013 This suggests that the observed interaction of almorexant with simvastatin is mainly caused by intestinal CYP3A4 inhibition, whereas the interaction with atorvastatin is more due to hepatic CYP3A4 inhibition. Simvastatin 63-74 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 106-112 23314529-2 2013 Metabolism of certain statins involves the cytochrome P450 3A (CYP3A) enzymes, and CYP3A4*22 significantly influences the dose needed for achieving optimal lipid control for atorvastatin, simvastatin, and lovastatin. Simvastatin 188-199 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 63-68 23492463-4 2013 Ranolazine is a weak inhibitor of CYP3A4 known to increase the serum level of simvastatin and its active metabolite 2-fold. Simvastatin 78-89 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 34-40 23314529-2 2013 Metabolism of certain statins involves the cytochrome P450 3A (CYP3A) enzymes, and CYP3A4*22 significantly influences the dose needed for achieving optimal lipid control for atorvastatin, simvastatin, and lovastatin. Simvastatin 188-199 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 83-89 21730017-7 2012 Repeated administration of SB-649868 dose-dependently increased exposure to simvastatin (10 mg), suggesting CYP3A4 inhibition ranging from very mild (5 mg) to strong (30 mg). Simvastatin 76-87 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 108-114 23252946-0 2013 Associations between the genotypes and phenotype of CYP3A and the lipid response to simvastatin in Chinese patients with hypercholesterolemia. Simvastatin 84-95 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 52-57 22451032-10 2012 Three clinical studies investigated the interaction showing simvastatin (CYP3A4 substrate) bioavailability reduced by TCZ and omeprazole bioavailability was decreased by TCZ-induced CYP2C19 activity. Simvastatin 60-71 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 73-79 22529023-7 2012 The CYP3A4 statins (i.e., simvastatin, atorvastatin and lovastatin) accounted for 85% of all statins in 2004, increasing to 93% in 2008. Simvastatin 26-37 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 4-10 22014153-1 2012 BACKGROUND AND PURPOSE: Imatinib, a cytochrome P450 2C8 (CYP2C8) and CYP3A4 substrate, markedly increases plasma concentrations of the CYP3A4/5 substrate simvastatin and reduces hepatic CYP3A4/5 activity in humans. Simvastatin 154-165 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 69-75 22237927-7 2012 Ninety-three percent of the patients were prescribed CYP3A4-metabolised statins, most whom received simvastatin (72%) and atorvastatin (24%). Simvastatin 100-111 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-59 22281720-1 2012 PURPOSE: Although CYP3A4/5 enzymes play the predominant role in the metabolism of simvastatin and lovastatin, polymorphisms in CYP2D6 were reported to be associated with the cholesterol-lowering effect and/or tolerability of simvastatin. Simvastatin 82-93 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 18-24 22237927-1 2012 PURPOSE: The co-administration of cytochrome P450 3A4 (CYP3A4) inhibitors with simvastatin or atorvastatin (CYP3A4-metabolised statins) is associated with increased statin exposure and can increase the risk of adverse drug reactions. Simvastatin 79-90 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 34-53 22237927-1 2012 PURPOSE: The co-administration of cytochrome P450 3A4 (CYP3A4) inhibitors with simvastatin or atorvastatin (CYP3A4-metabolised statins) is associated with increased statin exposure and can increase the risk of adverse drug reactions. Simvastatin 79-90 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 55-61 22014153-8 2012 CONCLUSIONS AND IMPLICATIONS: Imatinib is a potent mechanism-based inhibitor of CYP3A4 in vitro and this finding explains the imatinib-simvastatin interaction and suggests that imatinib could markedly increase plasma concentrations of other CYP3A4 substrates. Simvastatin 135-146 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 80-86 22014153-1 2012 BACKGROUND AND PURPOSE: Imatinib, a cytochrome P450 2C8 (CYP2C8) and CYP3A4 substrate, markedly increases plasma concentrations of the CYP3A4/5 substrate simvastatin and reduces hepatic CYP3A4/5 activity in humans. Simvastatin 154-165 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 135-141 22014153-1 2012 BACKGROUND AND PURPOSE: Imatinib, a cytochrome P450 2C8 (CYP2C8) and CYP3A4 substrate, markedly increases plasma concentrations of the CYP3A4/5 substrate simvastatin and reduces hepatic CYP3A4/5 activity in humans. Simvastatin 154-165 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 135-141 22176629-9 2012 Simvastatin, or other statins predominantly metabolized by CYP3A4, should not be co-administered with posaconazole. Simvastatin 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 59-65 21820929-6 2012 RESULTS: CYP3A4 was responsible for the metabolism of lovastatin, simvastatin and atorvastatin; fluvastatin depends on CYP2C9; P-glycoprotein is responsible for decreased atorvastatin, pravastatin, simvastatin and lovastatin concentrations. Simvastatin 66-77 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 9-15 21820929-6 2012 RESULTS: CYP3A4 was responsible for the metabolism of lovastatin, simvastatin and atorvastatin; fluvastatin depends on CYP2C9; P-glycoprotein is responsible for decreased atorvastatin, pravastatin, simvastatin and lovastatin concentrations. Simvastatin 198-209 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 9-15 23032911-7 2012 Simvastatin is a substrate of CYP3A4 enzyme. Simvastatin 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 30-36 23032911-8 2012 Clinical and pharmacological data, available in the published literature, allow the assumption that simvastatin may induce CYP3A4 and result in increased hepatoxicity of paracetamol. Simvastatin 100-111 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 123-129 21844990-13 2011 No significant clinical interaction or effect was observed, even with the use of atorvastatin or simvastatin, which are metabolized by CYP3A4 such as tacrolimus. Simvastatin 97-108 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 135-141 21946898-0 2011 Novel CYP3A4 intron 6 single nucleotide polymorphism is associated with simvastatin-mediated cholesterol reduction in the Rotterdam Study. Simvastatin 72-83 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 6-12 21946898-1 2011 OBJECTIVES: CYP3A4 is involved in the oxidative metabolism of many drugs and xenobiotics including the HMG-CoA reductase inhibitor simvastatin. Simvastatin 131-142 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 12-18 21946898-2 2011 The objective of this study was to investigate whether a new CYP3A4 functional single nucleotide polymorphism (SNP) in intron 6 (CYP3A4*22) modifies the effect of simvastatin on total cholesterol (TOTc) or LDL cholesterol (LDLc) reduction in a population-based cohort study. Simvastatin 163-174 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 61-67 21946898-2 2011 The objective of this study was to investigate whether a new CYP3A4 functional single nucleotide polymorphism (SNP) in intron 6 (CYP3A4*22) modifies the effect of simvastatin on total cholesterol (TOTc) or LDL cholesterol (LDLc) reduction in a population-based cohort study. Simvastatin 163-174 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 129-135 21946898-3 2011 METHODS: In a total of 80 incident simvastatin users, the association between the CYP3A4 intron 6 C>T SNP (rs35599367) and reduction in cholesterol levels was analyzed using linear regression analysis and adjusting for potential confounding factors. Simvastatin 35-46 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 82-88 21946898-4 2011 RESULTS: The CYP3A4*22 allele was associated with a trend towards a stronger simvastatin lipid-lowering response, as reflected by the greater reduction in both TOTc and LDLc levels when compared with homozygous wild type. Simvastatin 77-88 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 13-19 21946898-7 2011 CONCLUSION: The CYP3A4*22 intron 6 SNP T-variant allele was associated with reduced CYP3A4 activity, resulting in a better lipid lowering response to simvastatin, when data were adjusted for confounding factors. Simvastatin 150-161 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 16-22 21946898-7 2011 CONCLUSION: The CYP3A4*22 intron 6 SNP T-variant allele was associated with reduced CYP3A4 activity, resulting in a better lipid lowering response to simvastatin, when data were adjusted for confounding factors. Simvastatin 150-161 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 84-90 21883349-7 2011 Similarly, statins such as simvastatin are metabolized by CYP3A4, whereas others like pravastatin are not. Simvastatin 27-38 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 58-64 22912565-8 2012 Based on additional literature data on in vitro drug metabolism and inhibition potency, loratadine and simvastatin and tegaserod and promethazine were predicted to have a strong DDI through the CYP3A4 and CYP2D6 enzymes, respectively. Simvastatin 103-114 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 194-200 21443601-8 2011 The CYP3A4 +- PgP substrates of simvastatin and ciclosporin A did not affect the single or repeated dose PK of alitretinoin. Simvastatin 32-43 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 4-10 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. Simvastatin 136-147 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 27-33 21045169-9 2010 DISCUSSION: Simvastatin undergoes extensive first-pass metabolism mediated by CYP3A4, making it susceptible to significant drug interactions. Simvastatin 12-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 78-84 21105332-4 2010 In this review we present results of studies assessing effect of various allele variants of CYP3A4 and CYP3A5 on efficacy and tolerability of atorvastatin, lovastatin,, and simvastatin in different populations of patients. Simvastatin 173-184 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 92-98 20150526-1 2010 Diltiazem increases systemic exposure to simvastatin via inhibition of CYP3A. Simvastatin 41-52 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 71-76 20203109-8 2010 Buspirone, sildenafil, and simvastatin exhibited similar or greater sensitivity than midazolam to CYP3A4 inhibition in vivo. Simvastatin 27-38 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 98-104 20203109-9 2010 Finally, Simcyp was used to predict the in vivo magnitude of CYP3A4 DDIs caused by AMG 458 using midazolam, sildenafil, simvastatin, and testosterone as probe substrates. Simvastatin 120-131 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 61-67 19943026-3 2010 All protease inhibitors are inhibitors of CYP3A, which is important in the metabolism of approximately 50% of all drugs, e.g. simvastatin, atorvastatin, sildenafil, and clarithromycin. Simvastatin 126-137 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 42-47 18213452-0 2008 Pharmacokinetics of the CYP 3A substrate simvastatin following administration of delayed versus immediate release oral dosage forms. Simvastatin 41-52 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 24-30 20829626-7 2010 The use of ketoconazole, a potent inhibitor of cytochrome P450 3A4 (CYP3A4), may significantly increase plasma concentrations of certain statins (such as simvastatin and atorvastatin) that undergo metabolism by the same pathway, thus increasing the risk of complications and side effects. Simvastatin 154-165 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 47-66 20829626-7 2010 The use of ketoconazole, a potent inhibitor of cytochrome P450 3A4 (CYP3A4), may significantly increase plasma concentrations of certain statins (such as simvastatin and atorvastatin) that undergo metabolism by the same pathway, thus increasing the risk of complications and side effects. Simvastatin 154-165 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 68-74 20183988-17 2009 The risk is strongly intensified by drug interactions through CYP3A4 (for simvastatin and atorvastatin), high doses, and combination therapy with fibrates. Simvastatin 74-85 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 62-68 19429419-4 2009 Simvastatin lactone, but not the acid form, exhibited a strong inductive effect on the mRNA expression of MDR1 and CYP3A in a dose-dependent manner. Simvastatin 0-19 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 115-120 19206087-0 2009 Rhabdomyolysis reports show interaction between simvastatin and CYP3A4 inhibitors. Simvastatin 48-59 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 64-70 19206087-1 2009 PURPOSE: To assess spontaneous reports of rhabdomyolysis associated with simvastatin (SV) and pravastatin (PV) for evidence of CYP3A4 interaction. Simvastatin 73-84 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 127-133 19220274-3 2009 Simvastatin exhibits particularly high interaction potential due to substantial metabolism via cytochrome P450 3A4 (CYP3A4). Simvastatin 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 95-114 19220274-3 2009 Simvastatin exhibits particularly high interaction potential due to substantial metabolism via cytochrome P450 3A4 (CYP3A4). Simvastatin 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 116-122 19220274-15 2009 Considering the pronounced interaction potential of simvastatin with CYP3A4 inhibitors, a negative influence of the new policy on overall statin safety seems likely. Simvastatin 52-63 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 69-75 19802823-0 2010 Influence of genetic variation in CYP3A4 and ABCB1 on dose decrease or switching during simvastatin and atorvastatin therapy. Simvastatin 88-99 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 34-40 19802823-1 2010 PURPOSE: Simvastatin and atorvastatin are metabolized by the CYP3A4 enzyme and transported by the ABCB1 transporter. Simvastatin 9-20 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 61-67 19802823-6 2010 RESULTS: Simvastatin and atorvastatin users with the CYP3A4*1B variant G allele had a lower risk (HR 0.46; 95%CI 0.24-0.90) for these events than users with the wild-type AA genotype. Simvastatin 9-20 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-59 19802823-10 2010 CONCLUSION: In simvastatin and atorvastatin users, the CYP3A4*1B G allele is associated with a lower risk of elevated statin plasma levels, particularly in women and in users with the ABCB1 3435T variant allele. Simvastatin 15-26 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 55-61 18213452-2 2008 MATERIALS AND METHODS: To target drug release and to assess regional gastrointestinal absorption of the CYP 3A substrate simvastatin from the distal parts of the intestine, delayed release film coated tableted oral dosage forms were developed. Simvastatin 121-132 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 104-110 18558792-0 2008 Risk management of simvastatin or atorvastatin interactions with CYP3A4 inhibitors. Simvastatin 19-30 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 65-71 18783297-9 2008 Using this equation, the ICCYP3A4 was calculated for seven inducers (bosentan, carbamazepine, efavirenz, phenytoin, pioglitazone, rifampicin [rifampin], and St John"s wort [hypericum]) on the basis of the reduction in the AUC of a coadministered standard substrate of CYP3A4, such as simvastatin, in ten DDI studies. Simvastatin 284-295 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 27-33 18302447-4 2008 OBJECTIVE: To evaluate the incidence and clinical consequences of the use of lovastatin or simvastatin with concomitant CYP3A4 inhibitors and inducers, and with fibrates. Simvastatin 91-102 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 120-126 18302447-14 2008 CONCLUSION: Although the pharmacokinetic interactions between lovastatin or simvastatin and CYP3A4 inhibitors and inducers are substantial, their clinical relevance seems to be limited, at least with lower statin doses. Simvastatin 76-87 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 92-98 18558792-2 2008 OBJECTIVE: To detect co-prescriptions of CYP3A4 inhibitors with simvastatin or atorvastatin in community pharmacies and assess the risk-preventive actions taken by the prescribing physicians who were alerted about the co-prescription by the pharmacist. Simvastatin 64-75 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 41-47 18558792-7 2008 RESULTS: In total, 245 co-prescriptions of CYP3A4 inhibitors with simvastatin (134 events) or atorvastatin (111) were detected. Simvastatin 66-77 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 43-49 18558792-14 2008 CONCLUSION: Nine out of ten physicians changed prescriptions or monitored potential adverse effects when informed by community pharmacists about the risk associated with co-prescription of CYP3A4 inhibitors with simvastatin or atorvastatin. Simvastatin 212-223 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 189-195 16714062-6 2006 Among the statins, simvastatin, lovastatin and atorvastatin are metabolized by cytochrome P450 3A4 (CYP3A4) while fluvastatin is metabolized by CYP2C9. Simvastatin 19-30 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 79-98 17381388-8 2007 The interacting mechanism likely was inhibited cytochrome P450 (CYP) 3A4 metabolism and possibly P-glycoprotein transport of simvastatin as well. Simvastatin 125-136 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 47-72 17381388-9 2007 Previous reports of simvastatin-clarithromycin-related events involved additional drugs that inhibited CYP3A4 and P-glycoprotein. Simvastatin 20-31 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 103-109 18220561-3 2007 Linear relationships were found between midazolam and four CYP3A substrates: simvastatin, buspirone, triazolam and eplerenone. Simvastatin 77-88 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 59-64 17615423-9 2007 Simvastatin is metabolized by CYP3A4. Simvastatin 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 30-36 17615423-12 2007 In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors. Simvastatin 206-217 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 56-62 17304269-8 2007 Three studies had investigated the degree to which simvastatin and atorvastatin interact with a CYP3A4 inhibitor in the same population. Simvastatin 51-62 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 96-102 17304269-10 2007 INTERPRETATION: Interaction studies show that atorvastatin and simvastatin display differences in interaction potential toward warfarin and drugs inhibiting CYP3A4 metabolism. Simvastatin 63-74 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 157-163 17192506-1 2007 Simvastatin, a cholesterol-lowering agent, is mainly metabolized by CYP3A4/5. Simvastatin 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 68-74 17178259-4 2006 Simvastatin, lovastatin, and atorvastatin are metabolized by cytochrome P450 (CYP) 3A4 (simvastatin acid is also metabolized by CYP2C8); their plasma concentrations and risk of myotoxicity are greatly increased by strong inhibitors of CYP3A4 (eg, itraconazole and ritonavir). Simvastatin 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 61-86 17178259-4 2006 Simvastatin, lovastatin, and atorvastatin are metabolized by cytochrome P450 (CYP) 3A4 (simvastatin acid is also metabolized by CYP2C8); their plasma concentrations and risk of myotoxicity are greatly increased by strong inhibitors of CYP3A4 (eg, itraconazole and ritonavir). Simvastatin 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 235-241 16714062-6 2006 Among the statins, simvastatin, lovastatin and atorvastatin are metabolized by cytochrome P450 3A4 (CYP3A4) while fluvastatin is metabolized by CYP2C9. Simvastatin 19-30 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 100-106 16581329-6 2006 In persons taking simvastatin, lovastatin, or atorvastatin, 60% of cases involved drugs known to inhibit CYP3A4 (especially erythromycin and azole antifungals), and 19% involved fibrates, principally gemfibrozil. Simvastatin 18-29 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 105-111 16581325-4 2006 Drug metabolism studies show simvastatin and lovastatin to be especially sensitive to the inhibiting effects of other drugs on the cytochrome P-450 3A4 (CYP3A4) isoenzyme. Simvastatin 29-40 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 131-151 16581325-4 2006 Drug metabolism studies show simvastatin and lovastatin to be especially sensitive to the inhibiting effects of other drugs on the cytochrome P-450 3A4 (CYP3A4) isoenzyme. Simvastatin 29-40 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 153-159 16264203-3 2005 METHODS AND RESULTS: Of the 211 consecutive patients who underwent coronary stenting after pretreatment with clopidogrel, 114 were receiving a CYP3A4-metabolized statin (59 simvastatin and 55 atorvastatin, Group 1), and 37 were receiving a non-CYP3A4-metabolized statin (30 pravastatin and 7 fluvastatin, Group 2) whereas 60 patients were not taking any statins (Control). Simvastatin 173-184 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 143-149 16581329-5 2006 Incidence was higher (4.2 per 100,000 person-years) with lovastatin, simvastatin, or atorvastatin (which are oxidized by cytochrome P450 3A4 [CYP3A4], which is inhibited by many drugs) than pravastatin or fluvastatin (which are not oxidized by CYP3A4). Simvastatin 69-80 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 121-140 16581329-5 2006 Incidence was higher (4.2 per 100,000 person-years) with lovastatin, simvastatin, or atorvastatin (which are oxidized by cytochrome P450 3A4 [CYP3A4], which is inhibited by many drugs) than pravastatin or fluvastatin (which are not oxidized by CYP3A4). Simvastatin 69-80 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 142-148 16581329-5 2006 Incidence was higher (4.2 per 100,000 person-years) with lovastatin, simvastatin, or atorvastatin (which are oxidized by cytochrome P450 3A4 [CYP3A4], which is inhibited by many drugs) than pravastatin or fluvastatin (which are not oxidized by CYP3A4). Simvastatin 69-80 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 244-250 16537817-1 2006 OBJECTIVE: To describe the fifth reported instance, as of February 15, 2006, of a severe interaction between simvastatin and amiodarone and hypothesize inhibition of CYP3A4 as the major mechanism. Simvastatin 109-120 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 166-172 16537817-8 2006 DISCUSSION: Simvastatin is metabolized primarily by CYP3A4, and amiodarone is a recognized inhibitor of this enzyme. Simvastatin 12-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 52-58 16580903-1 2006 OBJECTIVE: Our objective was to compare simvastatin with the validated probe midazolam in the assessment of cytochrome P450 (CYP) 3A activity. Simvastatin 40-51 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 108-132 16580903-11 2006 CONCLUSIONS: Compared with midazolam, simvastatin is a nonvalidated, suboptimal probe for studying CYP3A drug interactions because of its lack of CYP3A specificity. Simvastatin 38-49 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 99-104 16415122-7 2006 The commonly prescribed drugs loperamide, amitriptyline, diltiazem, domperidone, lansoprazole, omeprazole, and simvastatin were identified by our in silico and in vitro screens as relatively potent inhibitors of CYP3A4 that have the potential to interact with cytotoxic agents to cause adverse effects, highlighting the likelihood of drug-drug interactions affecting chemotherapy treatment. Simvastatin 111-122 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 212-218 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. Simvastatin 169-180 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 210-216 16321621-0 2005 The role of common variants of ABCB1, CYP3A4, and CYP3A5 genes in lipid-lowering efficacy and safety of simvastatin treatment. Simvastatin 104-115 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 38-44 16238904-12 2005 Administration of telithromycin with drugs metabolized via CYP3A4 may result in increased exposure to the co-administered drug, as shown for simvastatin (5.3-fold) and midazolam (6-fold). Simvastatin 141-152 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 59-65 12817528-6 2003 Concomitant treatment with CYP3A4 substrates altered mean AUC0-5 h and mean Cmax for repaglinide by 1% and 17% (ethinyloestradiol/levonorgestrel), 2% and 27% (simvastatin), or 11% and 3% (nifedipine). Simvastatin 159-170 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 27-33 15679472-3 2005 Some statins (atorvastatin, lovastatin and simvastatin) also requires metabolism by the cytochrome P450 3A4 system. Simvastatin 43-54 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 88-107 15650881-0 2005 Ile118Val genetic polymorphism of CYP3A4 and its effects on lipid-lowering efficacy of simvastatin in Chinese hyperlipidemic patients. Simvastatin 87-98 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 34-40 15650881-10 2005 After oral intake of simvastatin 20 mg daily for 4 weeks, the change of serum lipids in CYP3A4*1/*1 and CYP3A4*1/*4 groups showed a significant difference, with a mean decrease in triglycerides and total cholesterol of 38.1 +/- 7.6% versus 25.1 +/- 8.3% (P = 0.034) and of 35.8 +/- 9.6% versus 22.0 +/-20.4% (P = 0.0015) (means +/- SD), respectively. Simvastatin 21-32 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 88-94 15650881-10 2005 After oral intake of simvastatin 20 mg daily for 4 weeks, the change of serum lipids in CYP3A4*1/*1 and CYP3A4*1/*4 groups showed a significant difference, with a mean decrease in triglycerides and total cholesterol of 38.1 +/- 7.6% versus 25.1 +/- 8.3% (P = 0.034) and of 35.8 +/- 9.6% versus 22.0 +/-20.4% (P = 0.0015) (means +/- SD), respectively. Simvastatin 21-32 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 104-110 15963098-8 2005 Patients already using CYP3A4 inhibitors more frequently received fluvastatin (OR = 1.80; 95% CI 1.11, 2.94), metabolized by non-CYP3A4 pathways, and atorvastatin (OR = 1.62; 95% CI 1.06, 2.47), which is metabolized by CYP3A4, than simvastatin. Simvastatin 232-243 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 23-29 15811174-9 2005 She had previously taken simvastatin which is metabolized by CYP3A4, without any sign and symptoms of rhabdomyolysis. Simvastatin 25-36 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 61-67 15650881-13 2005 CYP3A4*4 was an allelic variant related to a functional decrease of CYP3A4 activity, and *4 expression seemed to increase the lipid-lowering effects of simvastatin. Simvastatin 152-163 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 15650881-13 2005 CYP3A4*4 was an allelic variant related to a functional decrease of CYP3A4 activity, and *4 expression seemed to increase the lipid-lowering effects of simvastatin. Simvastatin 152-163 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 68-74 14612892-0 2003 Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia. Simvastatin 73-84 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 88-107 14612892-2 2003 The main purpose of this study was to evaluate the effect of the coadministration of imatinib on the pharmacokinetics of simvastatin, a probe CYP3A4 substrate. Simvastatin 121-132 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 142-148 14522569-4 2003 Since certain lipophilic statins (i.e. simvastatin, atorvastatin, lovastatin) are a substrate of CYP3A4, we were interested in potential drug interactions between clopidogrel and statins. Simvastatin 39-50 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 97-103 12433810-2 2002 Treatment of 2- to 3-day-old human hepatocyte cultures with 3 x 10(-5) M lovastatin, simvastatin, fluvastatin, or atorvastatin for 24 h increased the amounts of CYP2B6 and CYP3A mRNA by an average of 3.8- to 9.2-fold and 24- to 36-fold, respectively. Simvastatin 85-96 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 172-177 12603176-2 2003 PURPOSE: To investigate in vivo the mutual pharmacokinetic interactions between bosentan and simvastatin, a CYP3A4 substrate. Simvastatin 93-104 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 108-114 14727985-10 2002 Simvastatin and lovastatin are significantly metabolized by cytochrome P450 enzymes (CYP3A4) and are therefore not recommended for coadministration with protease inhibitors. Simvastatin 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 85-91 12410059-7 2002 In patients with chronic renal failure, co-administration of colchicine with simvastatin may accelerate the onset of myopathy because CYP3A4 (part of cytochrome P450) is crucial in the breakdown of both drugs. Simvastatin 77-88 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 134-140 11753267-11 2001 Because simvastatin is extensively metabolized by CYP3A4 in the intestinal wall and liver, which are induced by St John"s Wort, it is likely that this interaction is partly caused by the enhancement of the CYP3A4-mediated first-pass metabolism of simvastatin in the small intestine and liver. Simvastatin 8-19 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 50-56 11753267-11 2001 Because simvastatin is extensively metabolized by CYP3A4 in the intestinal wall and liver, which are induced by St John"s Wort, it is likely that this interaction is partly caused by the enhancement of the CYP3A4-mediated first-pass metabolism of simvastatin in the small intestine and liver. Simvastatin 8-19 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 206-212 11753267-11 2001 Because simvastatin is extensively metabolized by CYP3A4 in the intestinal wall and liver, which are induced by St John"s Wort, it is likely that this interaction is partly caused by the enhancement of the CYP3A4-mediated first-pass metabolism of simvastatin in the small intestine and liver. Simvastatin 247-258 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 50-56 11753267-11 2001 Because simvastatin is extensively metabolized by CYP3A4 in the intestinal wall and liver, which are induced by St John"s Wort, it is likely that this interaction is partly caused by the enhancement of the CYP3A4-mediated first-pass metabolism of simvastatin in the small intestine and liver. Simvastatin 247-258 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 206-212 11584328-7 2001 Several drugs have been shown to significantly inhibit the CYP3A4 pathway; in combination with statins such as lovastatin, simvastatin, atorvastatin, and cerivastatin, they have been shown to elevate serum concentrations of these statins, or may increase the risk of myopathy. Simvastatin 123-134 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 59-65 11550401-4 2001 Potent inhibitors of the cytochrome P450 3A4 (CYP3A4) enzyme increase the incidence of simvastatin toxicity. Simvastatin 87-98 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 25-44 11550401-4 2001 Potent inhibitors of the cytochrome P450 3A4 (CYP3A4) enzyme increase the incidence of simvastatin toxicity. Simvastatin 87-98 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 46-52 11497338-1 2001 OBJECTIVE: The objective of our study was to evaluate in humans the drug-drug interaction occurring during the concomitant administration of cisapride and simvastatin, two well-known substrates of CYP3A4. Simvastatin 155-166 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 197-203 11281188-4 2001 Both troglitazone and simvastatin are metabolized by cytochrome P-450 3A4. Simvastatin 22-33 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-73 11465417-9 2001 CONCLUSIONS: It was demonstrated that the competitive inhibition of CYP3A4-mediated simvastatin metabolism by itraconazole is the main cause of the drug interaction and that a Ki value corrected for drug adsorption to microsomes is the key factor in quantitatively predicting the maximum in vivo drug interactions. Simvastatin 84-95 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 68-74 11475198-4 2001 RESULT: More than 50% of the overall CYP metabolism is mediated through the isoenzyme CYP3A4, which is the main elimination route of simvastatin, lovastatin and atorvastatin. Simvastatin 133-144 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 86-92 11029845-8 2000 Lovastatin, simvastatin, and atorvastatin are substrates of CYP3A4, whereas fluvastatin is metabolized by CYP2C9. Simvastatin 12-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 60-66 11197581-9 2001 DISCUSSION: Clarithromycin is a potent inhibitor of CYP3A4, the major enzyme responsible for simvastatin metabolism. Simvastatin 93-104 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 52-58 11197581-12 2001 CONCLUSIONS: Macrolide antibiotics inhibit the metabolism of HMG-CoA reductase inhibitors that are metabolized by CYP3A4 (i.e., atorvastatin, cerivastatin, lovastatin, simvastatin). Simvastatin 168-179 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 114-120 11149552-9 2000 All of these drugs are cytochrome P450 3A4 and/or P-glycoprotein substrates that are known from previous pharmacokinetic studies to individually produce substantial increases in levels of simvastatin. Simvastatin 188-199 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 23-42 11075313-1 2000 Potential for inhibition of CYP3A activity by simvastatin, an HMG-CoA reductase inhibitor, was evaluated in 12 healthy male subjects who received placebo or 80 mg of simvastatin, the maximal recommended dose, once daily for 7 consecutive days. Simvastatin 46-57 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 28-33 11005703-12 2000 Atorvastatin, cerivastatin, lovastatin and simvastatin are predominantly metabolised by the CYP3A4 isozyme. Simvastatin 43-54 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 92-98 11180018-2 2000 The cholesterol-lowering drug simvastatin has an extensive first-pass metabolism, and it is partially metabolized by CYP3A4. Simvastatin 30-41 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 117-123 11180018-11 2000 Because the elimination half-life of simvastatin was not affected by rifampin, induction of the CYP3A4-mediated first-pass metabolism of simvastatin in the intestine and the liver probably explains this interaction. Simvastatin 37-48 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 96-102 11180018-11 2000 Because the elimination half-life of simvastatin was not affected by rifampin, induction of the CYP3A4-mediated first-pass metabolism of simvastatin in the intestine and the liver probably explains this interaction. Simvastatin 137-148 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 96-102 11180018-12 2000 Concomitant use of potent inducers of CYP3A4 can lead to a considerably reduced cholesterol-lowering efficacy of simvastatin. Simvastatin 113-124 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 38-44 34459464-6 2022 The clinical pharmacist found that the patient took nifedipine sustained-release tablets and simvastatin tablets simultaneously, and these medicines were all substrates of CYP3A4. Simvastatin 93-104 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 172-178 10741630-1 2000 BACKGROUND: Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase that is used as a cholesterol-lowering agent and is metabolized by cytochrome P450 3A (CYP3A) enzymes. Simvastatin 12-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 168-186 10741630-1 2000 BACKGROUND: Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase that is used as a cholesterol-lowering agent and is metabolized by cytochrome P450 3A (CYP3A) enzymes. Simvastatin 12-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 188-193 10741630-2 2000 Diltiazem is a substrate and an inhibitor of CYP3A enzymes and is commonly coadministered with cholesterol-lowering agents such as simvastatin. Simvastatin 131-142 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 45-50 10741630-9 2000 CONCLUSION: Diltiazem coadministration resulted in a significant interaction with simvastatin, probably by inhibiting CYP3A-mediated metabolism. Simvastatin 82-93 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. Simvastatin 70-81 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 59-64 10513779-3 1999 Simvastatin is a substrate for cytochrome P450 3A4 (CYP3A4). Simvastatin 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 31-50 10513779-3 1999 Simvastatin is a substrate for cytochrome P450 3A4 (CYP3A4). Simvastatin 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 52-58 10513779-4 1999 CYP3A4 inhibitors can elevate the plasma concentration of HMG-CoA reductase inhibitory activity derived from simvastatin. Simvastatin 109-120 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 9321523-13 1997 The results suggested that the in vivo inhibitory effects of SV on the metabolism of CYP3A substrates likely would be less than those of ketoconazole and itraconazole at their respective therapeutic concentrations. Simvastatin 61-63 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 85-90 34078115-6 2022 IL-6 inhibitors (sirukumab, tocilizumab, sarilumab) significantly enhance metabolism via CYP2C9 (s-warfarin), CYP2C19 (omeprazole), and CYP3A4 (simvastatin, midazolam) and reduce metabolism via CYP1A2 (caffeine). Simvastatin 144-155 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 136-142 11126989-3 2000 Most statins are metabolised by the CYP3A4 izoenzyme (lovastatin, simvastatin, atorvastatin, cerivastatin). Simvastatin 66-77 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 36-42 10665838-7 1999 Simvastatin, lovastatin, cerivastatin, and atorvastatin are biotransformed in the liver primarily by cytochrome P450-3A4, and are susceptible to drug interactions when co-administered with potential inhibitors of this enzyme. Simvastatin 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 101-120 10215754-3 1999 RESULTS: Mibefradil inhibited, in a concentration-dependent fashion, the metabolism of the four statins (simvastatin, lovastatin, atorvastatin and cerivastatin) known to be substrates for CYP3A. Simvastatin 105-116 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 188-193 9728898-11 1998 Concomitant administration of erythromycin, verapamil, or other potent inhibitors of CYP3A4 with simvastatin should be avoided. Simvastatin 97-108 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 85-91 9542477-0 1998 Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole. Simvastatin 0-11 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 76-82 34606062-6 2021 RESULTS: Multiple drug use involving either substrates and/or inhibitors of CYP3A4 and/or three or more drugs with the potential to cause acidosis explained the simvastatin-associated toxicity in 70.5% (n = 24) of cases. Simvastatin 161-172 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 76-82 33277702-5 2021 Azithromycin mildly inhibits simvastatin"s CYP 3A4 hepatic metabolism, and the SLCO1B1 polymorphism reduces simvastatin hepatic uptake. Simvastatin 29-40 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 43-50 33459228-7 2021 The statins like Simvastatin, Lovastatin, and Atorvastatin are substrates of CYP3A4 enzyme and P-glycoprotein and their concomitant use with the drugs inhibiting or inducing them would result in changes in plasma concentrations and toxicity/efficacy. Simvastatin 17-28 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 77-83 33237691-13 2000 One needs to be aware that certain drugs that are used to treat COVID-19 infections may interact with lipid lowering drugs. Remdesivir is metabolized by the Cyp3A4 pathway and statins that are also metabolized by this pathway should be avoided (atorvastatin, simvastatin, and lovastatin). Simvastatin 258-269 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 156-162 31640597-11 2019 Rhabdomyolysis was most likely induced by toxic plasma concentrations of Simvastatin due to Palbociclibs inhibition of the CYP3A4 enzyme in combination with a decreased hepatic uptake of Simvastatin due to single nucleotide polymorphism rs4149056. Simvastatin 73-84 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 123-129 32729746-3 2020 Potent inhibitors of cytochrome P450 (CYP) 3A4 significantly increase plasma concentrations of the active forms of simvastatin, lovastatin, and atorvastatin. Simvastatin 115-126 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 21-46 32351149-6 2020 We genotyped variants in simvastatin-metabolizing enzymes (CYP3A4/rs35599367 and CYP3A5/rs776746) and drug transporters (ABCB1/rs2032582 and SLCO1B1/rs4149056), and estimated their association with recurrence with logistic regression models.Results: We observed protective (though imprecisely-measured) associations between variants in genes encoding drug transporters (ABCB1 and SLCO1B1) and simvastatin-metabolizing enzymes (CYP3A4 and CYP3A5) and breast cancer recurrence in simvastatin-treated women. Simvastatin 25-36 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 59-65 30887238-4 2019 Moderate interactions [mean AUC fold change, <= 2.08 (midazolam) or 2.36 (simvastatin)] was predicted for CYP3A4 probe substrates and weak interactions (mean AUC fold change, <= 1.29-1.97) were predicted for CYP2C19, CYP2C9, and CYP2D6 substrates. Simvastatin 74-85 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 106-112