Metabolism of 8-iso-prostaglandin F2alpha.
Tritium labelled (x=1.1 MBq/17.7 microg/kg) and unlabelled 8-iso-PGF2alpha (43 microg/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-PGF2alpha 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-PGF2alpha, 15-keto-8-iso-PGF2alpha 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-PGF2alpha was identified as a major urinary metabolite.Thus, 8-iso-PGF2alpha metabolises in the rabbit mainly to several degraded polar metabolites through dehydrogenation at C-15, reduction of delta13-double bond and beta-oxidation, and excretes efficiently into the urine.
Basu
S
S
Department of Geriatrics, Faculty of Medicine, Uppsala University, Sweden. Samar.Basu@geriatrik.uu.se
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D015237:Dinoprost / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D028441:F2-Isoprostanes; D005260:Female; D007553:Isotope Labeling; D010084:Oxidation-Reduction; D011817:Rabbits; D014316:Tritium
D028441:F2-Isoprostanes; D014316:Tritium; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost