Metabolism of 8‐iso‐prostaglandin F_2α

Tritium labelled ( 1.1 MBq/17.7 μg/kg) and unlabelled 8-iso-PGF_2α (43 μg/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_2α 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_2α, 15-keto-8-iso-PGF_2α and β-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 β-oxidised products. α-Tetranor-15-keto-13,14-dihydro-8-iso-PGF_2α was identified as a major urinary metabolite.Thus, 8-iso-PGF_2α metabolises in the rabbit mainly to several degraded polar metabolites through dehydrogenation at C-15, reduction of Δ¹³-double bond and β-oxidation, and excretes efficiently into the urine.