Effects of schizandrin A on the activity of CYP3A in rat liver microsomes

Abstract

Abstract: AIM: To study the effects of schizandrin A on CYP3A by in vitro drug metabolism experiments. METHODS: Midazolam (MDZ)was adopted as a drug “probe” and a detection method of high-performance liquid chromatography (HPLC)was established, the rat liver microsome was as a carrier.The IC₅₀ value of schizandrin A by in vitro administration and related enzyme kinetic parameters on CYP3A were detected. RESULTS: The endogenous substances did not interfere with the determination in the incubation system. The method was fast, stable and had high sensitivity. The IC₅₀ of schizandrin A on MDZ metabolism in liver microsomes was 6.26 μmol/mL, and the enzyme kinetic parameters were as follows:K_m =15.77 μmol/L, K_i=5.5 μmol/mL. CONCLUSION: Schizandrin A is able to inhibit CYP3A activity in rat liver microsomes. The inhibition is mixed type, non-competitive and anticompetitive inhibition.

Key words: CYP3A, schizandrin A, midazolam, HPLC, enzyme kinetic parameters

CLC Number:

R965

SU Ming-wei, LI Wei-liang, LIU Hui-ming, XIN Hua-wen, WANG Nai-ping. Effects of schizandrin A on the activity of CYP3A in rat liver microsomes[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(11): 1275-1280.

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