In vitro inhibition of 4 anti-tumor traditional Chinese medicine injections on activities of 7 main cytochrome P450s in human liver microsome

Abstract

Abstract: AIM: To evaluate the inhibition of 4 anti-tumor traditional Chinese medicine injections on activities of 7 main cytochrome P450s CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4/5 in human liver microsome in vitro.METHODS: 4 anti-tumor traditional Chinese medicine injections were incubated with human liver microsomes in the presence of seven probe substrates of CYP450 isoforms, respectively. Using LC-MS/MS method simultaneous quantification of 7 probe substrate-derived metabolites acetaminophen(CYP1A2), hydroxy-bupropin(CYP2B6), n-desethyl-amodiaquine(CYP2C8), 4'-hydroxy-diclofenac(CYP2C9), 4'-hydroxy-mephenytoin(CYP2C19), dextrorphan(CYP2D6) and 1-hydroxy-midazolam(CYP3A) to determine the activity of 7 CYP450 isoforms. The inhibitory effects were evaluated with half maximal inhibitory concentration (IC₅₀) values.RESULTS: IC₅₀ value of Xiao-Ai-Ping injection on CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP3A4/5 was 0.51%, 1.34%, 1.42%, 0.93%, 1.09%, and 0.75%, respectively. IC₅₀ value of Ai-Di injection on CYP2C8 was 0.21%. IC₅₀ value of Xiao-Ai-Ping injection on CYP2D6 was 2.58%; IC₅₀ value of Ai-Di injection on CYP2B6, CYP2C9, CYP2C19, and CYP3A4/5 was 13.24%, 16.31%, 4.27%, and 3.73%, respectively; IC₅₀ value of Hua-Chan-Su injection on CYP1A2, CYP2B6, CYP2C8, and CYP2D6 was 3.50%,28.01%, 20.32%, and 32.59%, respectively; IC₅₀ value of Kang-Ai injection on CYP1A2, CYP2B6, CYP2C8, CYP2D6, and CYP3A4/5 was 2.55%, 15.32%, 1.44%, 1.72%, and 3.99%, respctively, IC₅₀ values of them were exceeded their daily-dose concentrations, totally. The activity inhibition rates of Ai-Di injection on CYP1A2 and CYP2D6; Hua-Chan-Su injection on CYP2C9, CYP2C19 and CYP3A4/5; Kang-Ai injection on CYP2C9 and CYP2C19, were less than 50% within their concentration rangs of determinations.CONCLUSION: In vitro, Xiao-Ai-Ping injection and Ai-Di injection show significant inhibitory effect on CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4/5 and CYP2C8, respectively, under normal dosage. Xiao-Ai-Ping injection, Ai-Di injection, Hua-Chan-Su injection and Kang-Ai injection show minor inhibitory effect on CYP2D6; CYP2B6, CYP2C9, CYP2C19, CYP3A4/5; CYP1A2, CYP2B6, CYP2C8, CYP2D6 and CYP1A2, CYP2B6, CYP2C8, CYP2D6, CYP3A4/5, respectively. Ai-Di injection, Hua-Chan-Su injection and Kang-Ai injection don't show inhibitory effect on CYP1A2, CYP2D6; CYP2C9, CYP2C19, CYP3A4/5 and CYP2C9, CYP2C19, respectively.

Key words: traditional Chinese medicine injection, human liver microsomes, cytochrome P450, CYP, inhibition, herb-drug interaction

CLC Number:

R965.2

LIU Li-ya, HAN Yong-long, YU Qi, ZHU Jin-hui, GUO Cheng. In vitro inhibition of 4 anti-tumor traditional Chinese medicine injections on activities of 7 main cytochrome P450s in human liver microsome[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(5): 522-527.

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