Quantitative Correlations Among CYP3A Sensitive Substrates and Inhibitors:Literature Analysis

Title: Quantitative Correlations Among CYP3A Sensitive Substrates and Inhibitors:Literature Analysis

Volume: 8 Issue: 8

Author(s): Isabelle Ragueneau-Majlessi, Xavier Boulenc, Clemence Rauch, Houda Hachad and Rene H. Levy

Affiliation:

Keywords: Cytochrome P450 CYP3A, drug-drug interactions, inhibition

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 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.

Cite this article as:

Ragueneau-Majlessi Isabelle, Boulenc Xavier, Rauch Clemence, Hachad Houda and Levy H. Rene, Quantitative Correlations Among CYP3A Sensitive Substrates and Inhibitors:Literature Analysis, Current Drug Metabolism 2007; 8 (8) . https://dx.doi.org/10.2174/138920007782798135