中国人群细胞色素P4502D6基因多态性对曲马多药代动力学的影响  

Influence of CYP2D6 genetic polymorphism on pharmacokinetics of tramadol in Chinese population

作　　者：李芹[1,2] 王睿[2] 郭雅[2] 裴斐[2] 

机构地区：[1]天津医科大学基础医学院药理教研室,天津300070 [2]解放军总医院临床药理药学研究室,北京100853

出　　处：《中国临床药理学杂志》2009年第4期302-307,共6页The Chinese Journal of Clinical Pharmacology

基　　金：国家863计划基金资助项目(2002AA2Z341L);天津市自然科学基金重点赞助项目(09JCZDJC21500);天津医科大学科学基金资助项目(2007ky06)

摘　　要：目的研究中国人群CYP2D6基因多态性对曲马多(镇痛药)药代动力学的影响。方法不同基因型中国健康志愿者随机分为4组:第1组CYP2D6*2W*10W,第2组:CYP2D6*2M*10W,第3组:CYP2D6*2M*10H,第4组:CYP2D6*2M*10M。各组单次口服曲马多100mg后,用高效液相色荧光检测法测定血和尿中曲马多及其M1代谢产物O-去甲基曲马多(M1)的浓度,研究不同基因型对曲马多药代动力学的影响。结果第2组曲马多及其M1的主要药代动力学参数与第1组相比没有显著性差异;第3组与第1组、第4组与第1组、第4组与第3组比较,主要药代动力学参数均有显著性差异(P<0.05),且呈基因剂量效应。结论CYP2D6*2对于曲马多的药代动力学过程没有影响;但CYP2D6*10可降低酶活性,且CYP2D6*10纯合子变异较杂合子变异对曲马多药代动力学的影响更大,呈基因剂量效应。Objective To investigate on influence of CYP2D6 genetic polymorphism on pharmacokinetics of tramadol in Chinese volunteers. Methods Adult healthy Chinese volunteers with different CYP2D6 genotypes were categorized into the following four groups： group 1： CYP2D6 ＊ 2W ＊ 10W, group 2：CYP2D6 ＊ 2M ＊ 10W, group 3： CYP2D6 ＊ 2M ＊ 10H, group 4：CYP2D6 ＊ 2M ＊ 10M. After oral administration of 100 mg tramadol, plasma and urine samples were collected from each subject at different time within 32 h. The plasma and urine concentrations of tramadol and its metabolite O - desmethyltramadol （M1 ） were determined by HPLC with fluorescence detection. Resuits The main pharmacokinetic parameters of tramadol and MI in group 2 were not significantly different from those in group 1. There are significant difference for the main pharmacokinetic parameters of tramadol and M1 between group 3 and group 1, group 4 and group 1, group 4 and group 3, respectively （ P 〈 0.05 ）. Conclusion The present results shown that CYP2D6 ＊ 2 has no influence on the pharmacokinetics of tramadol, but CYP2D6 ＊ 10 reduces CYP2D6 activity which leads to the change of phenotype, and the homozygotes has more significant influence on the pharmacokinetics of tramadol than the heterozygotes in Chinese population.

关 键 词：细胞色素P4502D6 曲马多 O-去甲基曲马多 药代动力学 高效液相色谱-荧光检测 

分 类 号：R969.1[医药卫生—药理学] R971.1[医药卫生—药学]