Relationship of CYP2D6 genetic polymorphisms and the pharmacokinetics of tramadol in Chinese volunteers.
OBJECTIVE
To investigate the relationship between CYP2D6 genetic polymorphisms and the pharmacokinetics of tramadol in Chinese volunteers.


METHODS
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.


CONCLUSIONS
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) 2.05 +/- 1.01, 2.13 +/- 0.83, 4.24 +/- 2.75 and 6.85 +/- 2.78, respectively, in CYP2D6*1/*1, CYP2D6*2/*2, CYP2D6*2/*10 and CYP2D6*10/*10 subjects, respectively.
Li
Q
Q
Department of Pharmacology, Tianjin Medical University, Tianjin, China.
Wang
R
R
Guo
Y
Y
Wen
S
S
Xu
L
L
Wang
S
S
D000284:Administration, Oral; D000328:Adult; D000701:Analgesics, Opioid / Q000493:pharmacokinetics*; D002681:China; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D014147:Tramadol / Q000031:analogs & derivatives / Q000493:pharmacokinetics*
D000701:Analgesics, Opioid; C080580:O-demethyltramadol; D014147:Tramadol; D019389:Cytochrome P-450 CYP2D6