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

Abstract

1. Absorption, biotransformation and elimination of [¹⁴C]oxaprotiline · HCl have been studied after oral administration of 50 mg doses to two human subjects.

2. 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.

3. Peak blood concn. of unchanged oxaprotiline were 16 and 19ng/ml before, and 167 and 207ng/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 (2ng equiv./ml), but also increased after hydrolysis (11—19ng equiv./ml).

4. Oxaprotiline was bound (83%) in vitro to serum proteins. Sixty per cent was bound to serum albumin and 20% to α₁-acid glycoprotein.

5. 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%.