The disposition and metabolism of the synthetic prostaglandin fluprostenol (ICI 81,008) in the horse

Abstract

1. Following single intramuscular doses of [¹⁴C]fluprostenol (0·5-2·4μg/kg) to three female horses and to three gelded male horses, radioactivity was present in the plasma within 5 min; peak concn. (0·32-1·30 ng/ml fluprostenol equiv.) occurred 5 to 90 min after injection. Radioactivity was still present in the plasma of the females after three days. About 88% of fluprostenol is bound to plasma proteins.

2. Radioactivity was present in the parotid saliva of the gelded male horses within 10 min. Peak concn. (45-91 pg/ml fluprostenol equiv.) occurred from 5 min to 1 h after injection. Saliva: plasma concn. ratios varied inversely with saliva flow rate and limiting ratios were 0·33 and 0·41 for the combined results of two experiments on each of two male horses; the calculated value is 0·46. Chromatography indicated that the majority of plasma and saliva radioactivity was [¹⁴C]fluprostenol.

3. Excretion of radioactivity in the urine was rapid and virtually complete 12h after dosing. The total radioactivity excreted in urine by the female horses was 45% of the dose (96 h) and by the gelded male horses 53% (30 h). About 30% of the radioactivity present in the urines was unchanged fluprostenol.

4. Faecal excretion, which was substantially complete after 2 days, accounted for 32% of the radioactivity administered to the female horses.

5. Tissue conc. of radioactivity in the female horses at four days were below the limits of detection (90pg/g), but 0·2-0·9% of the dose was detected at the site of injection.