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.
Keywords:
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.