Inhibition study of cytochrome P450 isozymes by (5R)-5-hydroxytriptolide using in vitro “cocktail” method

Abstract

Abstract: AIM: To evaluate whether 5-hydroxytriptolide (T8) is a direct inhibitior or time-dependent inhibitor of CYP3A/5, CYP2D6, CYP2C9, CYP1A2, CYP2C19, CYP2B6 and CYP2C8, and to evaluate the potential of drug-drug interaction with the substrates of above seven CYPs in clinical study, which provide a reference for clinical drug-drug interaction study.METHODS: IC₅₀ and IC₅₀ shift method were used in this study.RESULTS: The IC₅₀ of T8 on above seven CYPs was more than 100 μmol/L in direct inhibition experiment, and no IC₅₀ shift occurred in time-dependent inhibition experiment.CONCLUSION: T8 is neither a direct inhibitor nor time-dependent inhibitor of above seven CYPs, and the potential of drug-drug interaction caused by T8 inhibition on CYP450 isozymes is slim.

Key words: 5-hydroxytriptolide, CYP450, Direct inhibition, Time-dependent inhibition

CLC Number:

R965.2

LIU Hai-yan, ZHANG Le-duo, XIANG Zhi-xiong, MIAO Hong. Inhibition study of cytochrome P450 isozymes by (5R)-5-hydroxytriptolide using in vitro “cocktail” method[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(11): 1211-1218.

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