CYP2C9基因多态性对美洛昔康代谢动力学的影响  

Effect of CYP2C9 Genetic Polymorphism on the Pharmacokinetics of Meloxicam Metabolism in Chiness Subjects

作　　者：张梅[1] 许景峰[1] 杨永革[1] 徐林[1] 邸晓辉[1] 姜楠[1] 徐娟[1] 许雪廷[1] 

机构地区：[1]北京军区总医院药理科,北京100700

出　　处：《解放军药学学报》2012年第1期24-28,共5页Pharmaceutical Journal of Chinese People's Liberation Army

摘　　要：目的研究CYP2C9基因多态性对美洛昔康代谢动力学的影响。方法用焦磷酸测序法对24名健康受试者进行CYP2C9基因多态性检测;用LC-MS-MS法测定美洛昔康的血药浓度;用DAS2.0软件进行房室拟合及药代动力学参数计算,分析美洛昔康人体药代动力学特征,并比较CYP2C9*3突变型和野生型个体对美洛昔康代谢动力学特性的差异。结果 24名受试者中CYP2C9*3等位基因有2种表型(A/A,A/C),其中2名受试者为CYP2C9*3杂合突变型(A/C),其余为野生型(A/A);CYP2C9*3代谢美洛昔康的酶活性A/A﹥A/C。结论 CYP2C9基因多态性对美洛昔康的代谢具有显著影响,CYP2C9*3代谢美洛昔康的酶活性是A/A﹥A/C。检测突变型个体对指导美洛昔康临床个体化用药具有重要意义。Objective To investigate the effect of CYP2C9 polymorphism on the pharmacokinetics of meloxicam in Chinese healthy subjects.Methods The CYP2C9 genotypes of twenty-four Chinese healthy male subjects were selected by the pyrosequencing method.The subjects were genotyped with CYP2C9＊3 wild-type and mutation.HPLC-MS-MS method was used for the determination of meloxicam in plasma.The important pharmacokinetic parameters were caculated by DAS 2.0 software.The pharmacokinetics of meloxicam based on identification of genotypes（CYP2C9＊3 wild-type and mutation） was compared.Results Two kinds of CYP2C9＊3 phenotype existed in the subjects.CYP2C9＊ 3（A/A） was found in twenty-two subjects while CYP2C9＊3（A/C） in two subjects.For meloxicam,the A/A of CYP2C9＊3 alleles was more active than the A/C.Conclusion CYP2C9 genetic polymorphism has significant influence on the pharmacokinetics of meloxicam.A/A is more active than A/C.Pharmacogenomic studies will help rational and individualized medication.

关 键 词：美洛昔康 CYP2C9 等位基因 单核苷酸多态性 基因分型 

分 类 号：R969.1[医药卫生—药理学]