The metabolic fate of [14C]oxaprotiline.HCl in man. I. Disposition and preliminary pharmacokinetics.

Absorption, biotransformation and elimination of [14C]oxaprotiline.HCl have been studied after oral administration of 50 mg doses to two human subjects. Absorption was complete, and peak blood concn. of total 14C were 590 and 297 ng equiv./ml after 3-6 h in the two subjects. After 11 days, 84 and 90% dose was excreted in urine, and a total of 98% was excreted. Peak blood concn. of unchanged oxaprotiline were 16 and 19 ng/ml before, and 167 and 207 ng/ml after enzymic hydrolysis. The blood half-life in the two subjects was 23 and 29 h. The blood concn. of the desmethyl metabolite was low (2 ng equiv./ml), but also increased after hydrolysis (11-19 ng equiv./ml). Oxaprotiline was bound (83%) in vitro to serum proteins. Sixty per cent was bound to serum albumin and 20% to alpha 1-acid glycoprotein. In urine only 1% of total 14C was present as unchanged oxaprotiline, and 0.2% as the desmethyl metabolite. After enzymic hydrolysis these increased to 48 and 6%, respectively, and after acid hydrolysis to 85 and 10%.