THE METABOLIC-FATE OF [C-14]OXAPROTILINE.HCL IN MAN .2. ISOLATION AND IDENTIFICATION OF METABOLITES

The new antidepressant agent oxaprotiline is extensively metabolized by man. Following an oral 50 mg dose of racemic [14C]oxaprotiline, most of the 14C was excreted in the urine as metabolites [> 98% total 14C]; only 1% was excreted unchanged. Glucuronidation at the carbinol group of the molecule is the major metabolic pathway (83%). The 2 diastereoisomeric glucuronides were separated; the more polar O-glucuronide of S(+)-oxaprotiline predominates (44%), suggesting stereoselective disposition of the 2 enantiomers. Oxidative pathways are minor, and yield desmethyl oxaprotiline (10%) and 3-hydroxy R(-)-oxaprotiline (4%), both of which are conjugated with glucuronic acid. The biotransformation of oxaprotiline in man is less complex than that of other polycyclic antidepressants, which are metabolized mainly by oxidative reactions.