Pharmacokinetics of the enantiomers of trans‐tramadol and its active metabolite, trans‐O‐demethyltramadol, in healthy male and female chinese volunteers

Abstract

By using a high-performance capillary electrophoresis method, the pharmacokinetics of the enantiomers of trans-tramadol (trans-T) and its active metabolite, trans-O-demethyltramadol (M1), was studied in healthy male and female Chinese volunteers after oral administration of 100 mg trans-T hydrochloride. The values of Cmax for the enantiomers of trans-T and M1, and AUC0- infinity for (-)-trans T, (+)-M1, and (-)-M1 were higher in females than in males. The values of V(d)/F for the enantiomers of trans-T and CLr for (+)-M1 were lower in females than in males. The value of t(1/2) for (-)-M1 was longer in females than in males. There were significant differences in pharmacokinetic parameters of the two enantiomers of trans-T or M1 both in males and in females. The (+)/(-)-enantiomeric ratios of t(max), V(d)/F for trans-T in males were significantly different from those in females and the (+)/(-)-enantiomeric ratios of pharmacokinetic parameters for M1 in males were similar to those in females. There are gender-related differences in the pharmacokinetics of the enantiomers of trans-T and M1 which may be due to the greater body weights for men and/or the higher CYP2D6 activity in women. The pharmacokinetics of trans-T and M1 is stereoselective in men and women. There is a gender-related difference in the stereoselectivity in pharmacokinetics of trans-T in human and the stereoselectivity in pharmacokinetics of M1 in men is similar to that in women. Chirality 16:112-118, 2004.

Pharmacokinetics of tramadol and its three main metabolites in healthy male and female volunteers

“…By contrast Liu et al found a higher rate of O-demethylation of tramadol mediated by CYP2D6 resulting in higher C max and AUC of the metabolite (M1) in females than in males [9]. However, the results obtained in our study did not show a significant difference in non-stereoselective pharmacokinetic parameters of T and M1 between the two genders in our volunteers.…”

“…Up to now, the gender dependency of pharmacokinetics of tramadol and its main metabolites has not been investigated in detail. Liu et al showed that there is a gender related difference in the systemic exposure and related pharmacokinetic parameters of both enantiomers of tramadol and M1 in Chinese volunteers [9].…”

Enatiomeric determination of tramadol and O-desmethyltramadol in human urine by gas chromatography–mass spectrometry

“…As the drug undergoes a stereoselective metabolism, which is dependent on the activity of liver cytochrome P450 2D6, enantiomeric determination of T and ODT in urine may be reliably used as a simple noninvasive phenotyping test for the evaluation of CYP2D6 activity in vivo. Stereoselective determinations of T and ODT have been described using CE [33][34][35] or HPLC [36][37][38][39][40][41][42], but no GC method was described so far.…”

Effects of varying doses of tramadol on ketamine anaesthesia for laparocaecectomy in layer chickens

“…The lower but none significant respiratory rate of the birds in the TKL and TTKL groups may be associated with opiate characteristic of tramadol (Hui-Chen et al, 2004); although, tramadol is known to produce less respiratory depression when compared with other opiates (Hui-Chen et al, 2004). Birds under tramadol must have felt less pain through little or no sympathetic response resulting in a lower respiratory rate.…”