【摘 要】
：
To evaluate the effect of the cytochrome P450(CYP) 3A5 polymorphisms on the CYP3A activity and the activation of the clopidogrel in human liver S9 fraction.CYP3A5*3 genotypes of 40 liver tissues were
【机 构】
：
Medical Research Center of Guangdong General Hospital, Guangdong Provincial Cardiovascular Institute
【出 处】
：
2015年第一届药代动力学朝阳论坛
论文部分内容阅读
To evaluate the effect of the cytochrome P450(CYP) 3A5 polymorphisms on the CYP3A activity and the activation of the clopidogrel in human liver S9 fraction.CYP3A5*3 genotypes of 40 liver tissues were determined by the TaqMan allele discrimination assay.CYP3A enzyme activity was measured by a high performance liquid chromatography (HPLC) and the concentration of clopidogrel and its active metabolites (MP-H3, MP-H4) were measured by a HPLC-MS/MS method.The effect of the polymorphism on the CYP3A enzymes activity and the activation of clopidogrel was accessed.Of 40 liver tissues, the frequencies of CYP3A5*1/*1, CYP3A5*1/*3 and CYP3A5*3/*3 were 0.675, 0.25, and 0.075, respectively.Non-genetic factors, including gender, age, hypertension, had no significant influence on CYP3A enzyme activity in liver S9 fraction (P > 0.05).CYP3A activity and the concentrations of active metabolites MP-H4 of clopidogrel was significantly lower in liver S9 fraction with CYP3A5*3/*3 than that with CYP3A5*1/*1 or CYP3A5*1/*3 (P < 0.05).There was a significant positive correlation between the concentration of MP-H4 and CYP3A enzyme activity (r =0.435).The results indicated that the CYP3A5*3/*3 genotype could significantly reduce CYP3A enzyme activity and affect the activation of clopidogrel in liver tissues.
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