Stereoselectivity in renal clearance of trans-tramadol and its active metabolite, trans-O-demethyltramadol.

Abstract

AIM: To study the stereoselectivity in renal clearance of trans-tramadol and its active metabolite, trans-O-demethyltramadol. METHODS: The right kidneys were isolated from male SD rats and perfused with 100 mL of perfusate medium containing trans-tramadol 300 microg/L or trans-O-demethyltramadol 50 microg/L. After perfusion, the concentrations of the enantiomers of trans-tramadol and trans-O-demethyltramadol in the perfusate and urine were determined by high performance capillary electrophoresis. The enantiomeric ratios were calculated. RESULTS: After the kidneys being perfused with trans-tramadol hydrochloride, the concentration of (+)-trans-tramadol was higher than that of (-)-trans-tramadol, and the concentration of (+)-trans-O-demethyltramadol was lower than that of (-)-trans-O-demethyltramadol in the perfusate; meanwhile, (+)-trans-tramadol was more than (-)-trans-tramadol, and (+)-trans-O-demethyltramadol was less than (-)-trans-O-demethyltramadol in the urine. After the kidneys being perfused with trans-O-demethyltramadol, the concentration of (+)-trans- O-demethyltramadol was lower than that of (-)-trans-O-demethyltramadol in the perfusate, and (+)-trans-O-demethyltramadol was more than (-)-trans-O-demethyltramadol in the urine. CONCLUSION: The renal clearance of trans-tramadol was stereoselective. The O-demethylation of trans-tramadol was stereoselective in the kidneys, (-)-trans-tramadol being preferentially metabolized. The renal clearance of trans-O-demethyltramadol was also stereoselective, the (+)-enantiomer being preferentially cleared into the urine.