Gender-related differences in pharmacokinetics of enantiomers of trans-tramadol and its active metabolite, trans-O-demethyltramadol, in rats.
OBJECTIVE
To compare the pharmacokinetics of the enantiomers of trans-tramadol (trans-T) and its active metabolite, trans-O-demethyltramadol (M1), in male and female rats.


METHODS
Following a single oral dose of 10 mg/kg trans-T hydrochloride to rats, (+)-trans-T, (-)-trans-T, (+)-M1, and (-)-M1 in plasma were determined by a high performance capillary electrophoresis method.


RESULTS
The females showed higher plasma concentrations of (+)-trans-T, (-)-trans-T, and (+)-M1 than the males. The enantiomers of trans-T were absorbed and eliminated more slowly in the females than in the males. (+)-M1 was eliminated more slowly in the females than in the males. All pharmacokinetic parameters but Tmax of the two enantiomers of trans-T were significantly different in both sex rats. The (+)/(-)-enantiomeric ratios of the pharmacokinetic parameters for trans-T in the males were similar to those in the females. The values of Cmax, AUC(0-infinity) of the two enantiomers of M1 were significantly different in both sex rats. The (+)/(-)-enantiomeric ratios of Cmax, AUC(0-infinity) for M1 were lower than 1 in the males, larger than 1 in the females.


CONCLUSIONS
Systemic exposure of (+)-trans-T, (-)-trans-T, and (+)-M1 was higher in female rats than in male rats. The stereoselectivity in pharmacokinetics of trans-T was similar, and that of M1 was different in male and female rats.
Liu
Hui-Chen
HC
Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China. wangyl52@heinfo.net
Jin
Shu-Min
SM
Wang
Yong-Li
YL
D000818:Animals; D019540:Area Under Curve; D005260:Female; D008297:Male; D009294:Narcotics / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013237:Stereoisomerism; D014147:Tramadol / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*
D009294:Narcotics; C080580:O-demethyltramadol; D014147:Tramadol