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在大鼠体内反式曲马朵及其活性代谢物反式氧去甲基曲马朵对映体药代动力学的性别差异
AIM: 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, AUC0-∞ of the two enantiomers of M1 were significantly different in both sex rats. The (+)/(-)-enantiomeric ratios of Cmax, AUC0-∞ 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.
