Pharmacokinetic and tissue residue characteristics of fenprostalene, a prostaglandin F2 alpha analog, in swine

Fenprostalene, a prostaglandin F2 alpha analog, can be used to induce parturition in swine. As part of the approval process for that indication, pharmacokinetic characteristics of the absorption and elimination of fenprostalene and the depletion of drug residues from the principal edible tissues of swine were studied. Blood samples, urine, and feces were collected from 8 gilts (body weight, 95 +/- 1.7 kg) for up to 72 hours after a single dose of 0.5 mg of 13,14-[3H]-fenprostalene in polyethylene glycol-400 was administered SC. At intervals of 24, 48, 72, and 168 hours after dosing, 2 gilts each were killed, and samples of liver, kidney, muscle, and abdominal fat were obtained for analysis. The mean (+/- SEM) maximal concentration of fenprostalene radioequivalents in plasma (0.41 +/- 0.05 nanogram-equivalents/ml; n = 8) was observed at 12 hours and decreased biexponentially, with half-lives of approximately 8 hours and 9 days. Mean cumulative recovery (n = 4) of the administered dose by 72 hours was 61.2 +/- 5.9% in urine and 18.5 +/- 2.6% in feces. The highest tissue fenprostalene concentration was in kidneys and liver, probably reflecting the role of those organs in excreting fenprostalene. Rates of depletion of fenprostalene equivalents from the injection site, kidneys, and liver were comparable with those previously observed in cattle. The composition of residue in the liver of 2 gilts slaughtered 12 hours after SC administration of [3H]-fenprostalene was examined in a second study. Results suggested that approximately 4% of the total residue was pharmacologically potent fenprostalene or the carboxylic acid form of fenprostalene. Approximately 29% of the residue was extensively degraded to acidic metabolites. The remaining 67% was bound, nonextractable material.