Metabolism of 8-iso-prostaglandin F2α

Tritium labelled ((x) over bar=1.1 MBq/17.7 mu g/kg) and unlabelled 8-iso-PGF(2 alpha), (43 mu g/kg) were administered intravenously to female rabbits and frequent blood and continuous urinary samples were collected up to 4 h. The total radioactivity was lost rapidly from the circulation. About 80% of the total radioactivity was found in urine within 4 h. The plasma half-life of 8-iso-PGF(2 alpha) is found to be 1 min at the distribution phase. The terminal elimination phase half-life was about 4 min. At 1.5 min after administration 64%, 19% and 13% of the plasma radioactivity represented 8-iso-PGF(2 alpha), 15-keto-8-iso-PGF(2 alpha) and beta-oxidised products, respectively. The values for 20-min plasma were 5%, 2% and 88%. The radiochromatograms from 10 min-4 h urinary samples were dominated by more polar beta-oxidised products. alpha-Tetranor-15-keto-13,14-dihydro-8-iso-PGF(2 alpha) was identified as a major urinary metabolite. Thus, 8-iso-PGF(2 alpha) metabolises in the rabbit mainly to several degraded polar metabolites through dehydrogenation at C-15, reduction of Delta(13)-double bond and beta-oxidation, and excretes efficiently into the urine. (C) 1998 Federation of European Biochemical Societies.