Relationship of CYP2D6 genetic polymorphisms and the pharmacokinetics of tramadol in Chinese volunteers

P>Objective: To investigate the relationship between CYP2D6 genetic polymorphisms and the pharmacokinetics of tramadol in Chinese volunteers. Method: A gene chip was established for determining CYP2D6 genotype. Forty adult healthy Chinese subjects were categorized as: group 1, CYP2D6*1/*1; group 2, CYP2D6*2/*2; group 3, CYP2D6*2/*10; group 4, CYP2D6*10/*10. After oral administration of 100 mg tramadol, plasma and urine samples were collected over a 32-h period. Results: 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. Conclusion: CYP2D6*2 does not alter the pharmacokinetics of tramadol, whereas CYP2D6*10 did with homozygotes showing a more pronounced reduction than heterozygotes. The 32-h metabolic ratio of tramadol to M-1 were (mean +/- SD) 2 center dot 05 +/- 1 center dot 01, 2 center dot 13 +/- 0 center dot 83, 4 center dot 24 +/- 2 center dot 75 and 6 center dot 85 +/- 2 center dot 78, respectively, in CYP2D6*1/*1, CYP2D6*2/*2, CYP2D6*2/*10 and CYP2D6*10/*10 subjects, respectively.