Hui-chen Liu, Xi-Jie Zhang, Yan-Yan Yang
2002
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12
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Journal
Acta pharmacologica Sinica
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.