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A screening study of drug-drug interactions in cerivastatin users: an adverse effect of clopidogrel.
Monday,2013-01-14 16:57 America/Los_Angeles — poolea2
| Title | A screening study of drug-drug interactions in cerivastatin users: an adverse effect of clopidogrel. |
| Publication Type | Journal Article |
| Year of Publication | 2012 |
| Authors | Floyd, JS, Kaspera, R, Marciante, KD, Weiss, NS, Heckbert, SR, Lumley, T, Wiggins, KL, Tamraz, B, Kwok, P-Y, Totah, RA, Psaty, BM |
| Journal | Clin Pharmacol Ther |
| Volume | 91 |
| Issue | 5 |
| Pagination | 896-904 |
| Date Published | 2012 May |
| ISSN | 1532-6535 |
| Keywords | Adverse Drug Reaction Reporting Systems, Aged, Aged, 80 and over, Aryl Hydrocarbon Hydroxylases, Case-Control Studies, Cytochrome P-450 CYP2C8, Cytochrome P-450 CYP3A, Cytochrome P-450 CYP3A Inhibitors, Drug Interactions, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Male, Platelet Aggregation Inhibitors, Pyridines, Rhabdomyolysis, Ticlopidine |
| Abstract | <p>An analysis of a case-control study of rhabdomyolysis was conducted to screen for previously unrecognized cytochrome P450 enzyme (CYP) 2C8 inhibitors that may cause other clinically important drug-drug interactions. Medication use in cases of rhabdomyolysis using cerivastatin (n = 72) was compared with that in controls using atorvastatin (n = 287) for the period 1998-2001. The use of clopidogrel was strongly associated with rhabdomyolysis (odds ratio (OR) 29.6; 95% confidence interval (CI), 6.1-143). In a replication effort that used the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS), it was found that clopidogrel was used more commonly in patients with rhabdomyolysis receiving cerivastatin (17%) than in those receiving atorvastatin (0%, OR infinity; 95% CI = 5.2-infinity). Several medications were tested in vitro for their potential to cause drug-drug interactions. Clopidogrel, rosiglitazone, and montelukast were the most potent inhibitors of cerivastatin metabolism. Clopidogrel and its metabolites also inhibited cerivastatin metabolism in human hepatocytes. These epidemiological and in vitro findings suggest that clopidogrel may cause clinically important, dose-dependent drug-drug interactions with other medications metabolized by CYP2C8.</p> |
| DOI | 10.1038/clpt.2011.295 |
| Alternate Journal | Clin. Pharmacol. Ther. |
| PubMed ID | 22419147 |
| PubMed Central ID | PMC3830936 |
| Grant List | T32 HL007902 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States HL085251 / HL / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States R01 HL085251 / HL / NHLBI NIH HHS / United States R01 HL078888 / HL / NHLBI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States T32HL007902. / HL / NHLBI NIH HHS / United States N01-HC45133 / HC / NHLBI NIH HHS / United States N01-HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States HL078888 / HL / NHLBI NIH HHS / United States R01HL087652 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States |