Department of Pharmacology, Tianjin Medical University, Tianjin, China.
J Clin Pharm Ther. 2010 Apr;35(2):239-47. doi: 10.1111/j.1365-2710.2009.01102.x.
To investigate the relationship between CYP2D6 genetic polymorphisms and the pharmacokinetics of tramadol in Chinese volunteers.
A gene chip was established for determining CYP2D6 genotype. Forty adult healthy Chinese subjects were categorized as: group 1, CYP2D6*1/1; group 2, CYP2D62/2; group 3, CYP2D62/10; group 4, CYP2D610/*10. After oral administration of 100 mg tramadol, plasma and urine samples were collected over a 32-h period.
The main pharmacokinetic parameters of tramadol and its metabolite O-demethyltramadol (M(1)) in groups 1 and 2 were not significantly different. However, they were significantly different between groups 3 and 1, groups 4 and 1 and groups 4 and 3.
CYP2D62 does not alter the pharmacokinetics of tramadol, whereas CYP2D610 did with homozygotes showing a more pronounced reduction than heterozygotes. The 32-h metabolic ratio of tramadol to M(1) were (mean +/- SD) 2.05 +/- 1.01, 2.13 +/- 0.83, 4.24 +/- 2.75 and 6.85 +/- 2.78, respectively, in CYP2D6*1/1, CYP2D62/2, CYP2D62/10 and CYP2D610/*10 subjects, respectively.
研究细胞色素 P4502D6（CYP2D6）基因多态性与中国志愿者曲马多药代动力学的关系。
建立基因芯片以确定 CYP2D6 基因型。将 40 名成年健康中国志愿者分为 4 组：CYP2D6*1/1 组（组 1）、CYP2D62/2 组（组 2）、CYP2D62/10 组（组 3）和 CYP2D610/*10 组（组 4）。志愿者口服 100mg 曲马多后，在 32 小时内采集血浆和尿液样本。
组 1 和组 2 中曲马多及其代谢物 O-去甲基曲马多（M1）的主要药代动力学参数无显著差异。然而，组 3 与组 1、组 4 与组 1 以及组 4 与组 3 之间存在显著差异。
CYP2D62 不改变曲马多的药代动力学，而 CYP2D610 则改变了其药代动力学，杂合子与纯合子相比，其代谢产物的减少更为明显。CYP2D6*1/1、CYP2D62/2、CYP2D62/10 和 CYP2D610/*10 组的曲马多与 M1 的 32 小时代谢比分别为（均数±标准差）2.05±1.01、2.13±0.83、4.24±2.75 和 6.85±2.78。
