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  • Title: Quantitative correlations among CYP3A sensitive substrates and inhibitors: literature analysis.
    Author: Ragueneau-Majlessi I, Boulenc X, Rauch C, Hachad H, Levy RH.
    Journal: Curr Drug Metab; 2007 Dec; 8(8):810-4. PubMed ID: 18220561.
    Abstract:
    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, 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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