期刊
CURRENT DRUG METABOLISM
卷 8, 期 8, 页码 810-814出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/138920007782798135
关键词
cytochrome P450CYP3A; drug-drug interactions; inhibition
As a follow-up to the new classification of CYP3A inhibitors, the present work was undertaken to search for quantitative correlations of AUC ratios between sensitive substrates and midazolam (reference). A large set of clinical studies was obtained utilizing the M&T Drug Interaction Database (TM), and recent Product Labels. Linear relationships were found between midazolam and four CYP3A substrates: simvastatin, buspirone, triazolam and eplerenone. Simvastatin and buspirone were consistently more sensitive than midazolam, independent of the inhibitor. Quantitative correlations of AUC ratios between four CYP3A inhibitors (fluconazole, erythromycin, verapamil, diltiazem) and ketoconazole (400 mg/day) were also uncovered. The average potencies of these inhibitors relative to ketoconazole were 27% for erythromycin, 17% for fluconazole and 19% for verapamil.
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