细胞色素P450(CYP)3A5与CYP2C19基因多态性对伏立康唑在健康人体的药代动力学特征的影响

摘要

Objective To study the effect of cytochrome P450(CYP) 3A5, CYP2C19 gene polymorphism in Chinese healthy human on the pharmacokinetics of voriconazole. Methods Genotyping of CYP3A5 and CYP2C19 was made with the method of RFLP - PCR targeted in healthy volunteers' blood. An LC - MS method for the determination of voriconazole in plasma was established. After a single oral dose 200 mg voriconazole tablets, the concentration of voriconazole plasma was determinatied using the above LC - MS method. Results The main pharmacokinetic parameters of AUC0-36 AUC0-∞ of CYP2C19 homozygous was notable higher than wild type and the heterozygous. The parameter of CL/F was notable lower than the wild type at dose of 200 mg. But the parameters of T1/2, Cmax had no statistical differences. CYP3A5 gene polymorphism had no statistical differences on pharmacokinetic parameters of voriconazole. Conclusion CYP2C19 gene polymorphism do affect the pharmacokinetic parameters of voriconazole and CYP3A5 gene polymorphism do not affect the pharmacokinetic parameters of voriconazole.%目的 研究中国健康人体内细胞色素P450(CYP)3A5、CYP2C19基因多态性对伏立康唑药代动力学的影响.方法 用RFLP-PCR法对受试者进行全血CYP3A5、CYP2C19基因分型；建立人血浆中伏立康唑的LC-MS测定方法,检测血药浓度；并对受试者单次口服伏立康唑200mg后的系列血药浓度进行测定.结果 伏立康唑200mg,CYP2C19突变纯合子的AUC0-36、AUC0-∞值均显著高于野生组；也显著高于突变杂合组；而CL/F值则明显低于野生组.T1/2口、Cmax等在各组间无统计学差异；伏立康唑各药代动力学参数在CYP3A5各组间均无统计学差异.结论 中国人体内CYP2C19基因多态性对伏立康唑的药代动力学过程有显著影响；而CYP3A5基因多态性对伏立康唑的药代动力学过程无明显影响.