Effects of 20 Chinese patent medicines on the catalytic activities of five main cytochrome P450s of human liver microsome

Key words: 
• Chinese patent medicine /
• human liver microsome /
• drug metabolism enzyme /
• inhibition

Abstract: Objective :The effects of the 20 Chinese Patent Medicines on the catalytic activities of five main drug metabolism enzymes of human liver microsome,CYP1A2,CYP2C9,CYP2C19,CYP2D6 and CYP 3A4,were assessed. Methods : Human liver microsome incubation experiment was carried out to assay the injection on the catalytic activities of the enzymes.Phenacetin,tolbutamide,S-mephenytoin,dextromethorphane and midazolam were used as the substrates of the enzymes.After the incubation,the five metabolites of the substrates were quantified by HPLC-MS/MS method.The inhibition was calculated by comparing the formation velocities of metabolites with or without test drug. Results : Liu Shen Pill showed obvious inhibitory effect on CYP1A2 with an IC₅₀ of 28.75 μg/mL;Gan Su Granule showed obvious inhibitory effect on CYP2C19 with an IC₅₀ of 29.80 μg/mL;Dan Shen Tablet showed obvious inhibitory effect on CYP1A2 with an IC₅₀ of 48.55 μg/mL;Bei Ling Capsule showed obvious inhibitory effect on CYP1A2 with an IC₅₀ of 17.45 μg/mL;Xia Tian Wu Compound Tablet showed obvious inhibitory effect on CYP2D6 with an IC₅₀ of 40.26 μg/mL;Tanshinone Capsule showed obvious inhibitory effects on CYP1A2,CYP2C9,CYP2C19,CYP2D6 and CYP3A4 with IC₅₀s of 7.04,13.97,55.77,33.90 and 34.57 μg/mL.Tong Feng Ding Capsule showed obvious inhibitory effect on CYP2D6 with an IC₅₀ of 37.56 μg/mL. Conclusion :Most test drugs showed obvious inhibitory effect on the catalytic activities of drug metabolism enzymes.The result indicated that Chinese Patent Medicine had the potential to induce drug-drug interactions and special attention should be paid when they are used in combined with other drugs.