Pharmacokinetics, disposition, and metabolism of bicifadine in humans

Bicifadine [DOV 220,075; (+/-)-1-(4-methylphenyl)-3-azabicyclo-[3.1.0]hexane HCl)] is a non-narcotic analgesic that has proven to be effective for the treatment of acute pain in clinical studies. The pharmacokinetics, disposition, and metabolism of bicifadine were determined in eight healthy adult male subjects following a single oral dose of 200 mg of [(14)C]bicifadine in solution. The maximum concentration of total drug equivalents and bicifadine in plasma was at approximately 1 h; the elimination half-life was 2.6 and 1.6 h for radioactivity and bicifadine, respectively. Unchanged bicifadine represented 15% of the area under the concentration-time curve for total drug equivalents; the rest was due mainly to the lactam (M12), the acid (M3), and the lactam acid (M9). Total recovery of the dose was 92%, with most of the radioactivity recovered in the urine in the first 24 h; fecal excretion accounted for only 3.5% of the dose. Approximately 64% of the dose was metabolized to M9 and its acyl glucuronide; another 23% was recovered as M3 and its acyl glucuronide. Neither bicifadine nor M12 were detected in urine or feces. There were no reported serious or severe adverse events during the study.