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


CONCLUSIONS
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.
Liu
Hui-Chen
HC
Department of Clinical Pharmacology, Bethune International Peace Hospital, Shijiazhuang 050082, China. lhc1@heinfo.net
Zhang
Xi-Jie
XJ
Yang
Yan-Yan
YY
Wang
Na
N
Hou
Yan-Ning
YN
D000701:Analgesics, Opioid / Q000493:pharmacokinetics* / Q000652:urine; D000818:Animals; D019075:Electrophoresis, Capillary / Q000379:methods; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014147:Tramadol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000652:urine*
D000701:Analgesics, Opioid; C080580:O-demethyltramadol; D014147:Tramadol