Pre-systemic metabolism of viprostol in the monkey following oral and topical administration

1. 14C-Viprostol, (I), a synthetic PGE2 analogue, was administered to 6 monkeys, orally, topically and intravenously in a three way crossover study. Total radioactivity and the pharmacologically active acid formed by rapid hydrolysis of viprostol in vivo, (II), were measured in plasma to determine absorption and absolute bioavailability. 2. After oral dosing approx. 31% of drug-related radioactivity was absorbed. Systemic bioavailability of unchanged active acid was only 7.3%. This indicates significant first-pass metabolism after oral administration, since only 23% of the absorbed radioactivity was available as 'unchanged' active drug (II). 3. After topical dosing, transdermal absorption of total radioactivity by 48 h averaged only 5% of dose. Absolute bioavailability of II averaged 3.8% of dose. This indicates that after transdermal absorption 74% of the absorbed radioactivity was available systemically as the active acid II, with the remainder being subject to pre-systemic metabolism.