In vitro prediction of CYP-mediated inhibitory drug and drug interaction

Abstract

Abstract: Cytochrome P450 (CYP)-mediated inhibitory drug and drug interaction(DDI)potential must be well evaluated during the course of drug discovery and development .It is not uncommon that drug inhibition of CYPs may lead to severe prescribing restrictions, or withdrawal of drugs from market .Not only may this kind of DDI jeopardize patients' safety , but also cause huge financial losses for drugmakers. In vitro strategy , due to its simplicity and high throughput possibility , has been routinely used to evaluate the potential of CYP-mediated DDI .However , in vitro data only provide indirect information. For this reason, in vitro inhibition data are frequently used to predict in vivo CYP-mediated inhibitory DDI potential .Further, such predicted data can be taken into consideration in designing clinical trials.In recent years, this field has undergone rapid development .The purpose of this re-view was to present the fundamentals, predictive strategies, and essential considerations in predicting in vivo DDI properties from in vitro data.

Key words: cytochrome P450, drug-drug interaction, reversible inhibition, irreversible inhibition, mech-anism-based inhibition

CLC Number:

R969

GUO Jian-jun, ZHAO Hua, WANG Jing-jing. In vitro prediction of CYP-mediated inhibitory drug and drug interaction[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(8): 841-848.

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