Absorption, tissue distribution, and excretion of 3H-labeled arbaprostil in the male rat

Abstract

A single dose of arbaprostil-11 beta-3H (4 micrograms/kg) was administered orally to male rats. A maximum plasma radioactivity concentration equivalent to 2.5 to 2.8 nanograms of the prostaglandin per ml was reached at 30 minutes and was maintained until 120 minutes after drug administration. The plasma drug disappearance half-life was 2.6 hours. These results along with data from tissue distribution studies suggested a rapid uptake of radiolabeled arbaprostil by the glandular stomach tissue followed by an apparent zero-order release of drug-related radioactivity from this tissue "reservoir" into the plasma. Drug-related radioactivity was excreted rapidly, with 96 to 99% of the urinary excretion and 82 to 97% of the fecal excretion being completed within 24 hours. A total of 49.6 +/- 3.5% of the orally administered dose was excreted in the urine and 46.7 +/- 3.9% in the feces. No radioactive residues were detected in the animals at the end of the 120 hour specimen collection period. The metabolic stability of the 11 beta-tritium label and the suitability of arbaprostil-3H for use in human studies was demonstrated.