Inhibitory effects of curcumin on activity of cytochrome P450 2C9 enzyme in human and 2C11 in rat liver microsomes. (April 2015)

• Record Type: Journal Article
• Authors: Wang, Zhe; Sun, Wei; Huang, Cheng-Ke; Wang, Li; ia, Meng-Ming; Cui, Xiao; Hu, Guo-Xin; Wang, Zeng-Shou
• Is Part Of: Drug development and industrial pharmacy. Volume 41:Number 4(2015:Apr.)
• Page Start: 613
• Page End: 616
• Publication Date: 2015-04
• Subjects: Pharmaceutical chemistry -- Periodicals; Pharmaceutical industry -- Periodicals; Drug Industry -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615.05
• DOI: 10.3109/03639045.2014.886697
• Languages: English
• ISSNs: 0363-9045

Abstract

<abstract> <title>Abstract</title> <p>Cytochrome P450 2C9 (CYP2C9), one of the most important phase I drug metabolizing enzymes, could catalyze the reactions that convert diclofenanc into diclofenac 4′-hydroxylation. Evaluation of the inhibitory effects of compounds on CYP2C9 is clinically important because inhibition of CYP2C9 could result in serious drug–drug interactions. The objective of this work was to investigate the effects of curcumin on CYP2C9 in human and cytochrome P450 2C11 (CYP2C11) in rat liver microsomes. The results showed that curcumin inhibited CYP2C9 activity (10 µmol L^–1 diclofenac) with half-maximal inhibition or a half-maximal inhibitory concentration (IC50) of 15.25 µmol L^–1 and Ki = 4.473 µmol L^–1 in human liver microsomes. Curcumin's mode of action on CYP2C9 activity was noncompetitive for the substrate diclofenanc and uncompetitive for the cofactor NADPH. In contrast to its potent inhibition of CYP2C9 in human, diclofenanc had lesser effects on CYP2C11 in rat, with an IC50 ≥100 µmol L^–1. The observations imply that curcumin has the inhibitory effects on CYP2C9 activity in human. These <italic>in vitro</italic> findings suggest that more attention should be paid to special clinical caution when intake of curcumin combined with other drugs in treatment.</p> </abstract>