Gender Dependency in Streoselective Pharmacokinetics of Tramadol and Its Phase I Metabolites in Relation to CYP2D6 Phenotype in Iranian Population.

Abstract

The stereoselective pharmacokinetic of Tramadol (T) and its main metabolites concerning the influence of CYP2D6 phenotype and gender on the phase I metabolism of this compound was studied after administration of 100 mg single oral dose of racemic T to 24 male and female subjects. The pharmacokinetic parameters were estimated from plasma concentrations of the analytes enantiomers. The metabolic ratio of T enantiomers was used for CYP2D6 phenotype determination. The plasma concentrations of both tramadol enantiomers were considerably higher in Poor metabolizers (PM) than in extensive metabolizers (EM), resulting in 43% and 37% increase in AUC values of (+)-T and (-)-T respectively. The plasma concentrations of the (+)- and (-)-M1 enantiomers in EMs were significantly higher than the respective concentrations in PMs. The N-demethylation pathway was indirectly affected by CYP2D6 phenotypic differences. The plasma concentration of both enantiomers of M2 in PMs was higher than Ems. Although the concentration profiles and most of the calculated pharmacokinetic parameters of T and its main metabolites appears to be different in EMs and PMs, only the stereoselectivity of M1 enantiomers was significantly different in relation to CYP2D6 subgroups. No significant gender-related difference in the pharmacokinetics of T and its metabolites was observed.