DISPOSITION OF THE SYNTHETIC PROSTAGLANDIN ANALOG CLOPROSTENOL (ESTRUMATE) IN THE RAT AND MARMOSET

1. Following subcutaneous administration of the synthetic prostaglandin analogue [14C]cloprostenol to the rat (200μg/kg), the dose was quantitatively recovered from the excreta: 52% of the dose was present in the urine and 43% in faeces. After intravaginal administration (200 μg/kg) 42% of the dose was recovered from the excreta, equally divided between urine and faeces, and 40% (range 25-66% of the dose was recovered from the site of application. The radiolabelled compounds present in faeces were eliminated initially via the bile. 2. The max. observed plasma concn. of total 14C in the rat was 84 ng equiv./ml at 30 min after subcutaneous administration of cloprostenol (200 μg/kg). A component which co-chromatographed with cloprostenol on t.l.c. was rapidly cleared from plasma with a half-life of 54 min. After intravaginal administration of cloprostenol (200 μg/kg), low and persistent plasma concn. of 14C were detected. 3. The metabolic fate of cloprostenol in the rat and marmoset has been studied with radiolabelled and non-labelled drug mixed such that fragments detected by mass spectrometry exhibited characteristic 12C: 14C isotope clusters. Metabolites derived from cloprostenol contained these characteristic doublets. 4. In the rat cloprostenol is metabolized by oxidation to tetranor-cloprostenol. Unchanged cloprostenol and a conjugate of tetranor-cloprostenol were minor urinary metabolites. In the rat biotransformation of cloprostenol in the cyclopentane ring occurred; the tetranor acid of 9-keto-cloprostenol was identified in urine. In the marmoset unchanged cloprostenol and dinor-cloprostenol were major urinary components. © 1979 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.