METABOLISM OF PROSTACYCLIN .3. URINARY METABOLITE PROFILE OF 6-KETO PGF1-ALPHA IN RAT

The in vivo metabolism of 6-keto PGF1α was investigated in rats. Following continuous intravenous infusion for 14 days the urinary metabolites were isolated and identified. A substantial amount of unchanged 6-keto PGF1α was recovered in the urine. The metabolic pattern very closely resembles that of PGI2 in rats. Metabolites were found which represented 15-dehydrogenation, β-oxidation, ω and ω-1-hydroxylation and oxidation. Previous work showed that 6-keto PGF1α is very poorly oxidized by 15-PGDH. We administered 15-[H3]-PGI2 and 15-[H3]-6-keto PGF1α to rats and measured urinary tritiated water as an index for in vivo 15-PGDH activity. The results showed that PGI2 and 6-keto PGF1α were both oxidized to the 15-keto product, although the rate of oxidation of PGI2 was greater than that of 6-keto PGF1α. We concluded that the administered PGI2 was oxidized by 15-PGDH before hydrolysis to 6-keto PGF1α. A portion of the dose is probably hydrolyzed before 15-dehydrogenation. © 1979.