Metabolism of 16, 16-dimethyl-trans-delta 2-prostaglandin E1 methyl ester (ONO-802) following intravenous and vaginal administration to pregnant women.

Following iv and vaginal administration of (5,6-3H2)-ONO-802 (5,6-3H2-16, 16-dimethyl-trans-delta 2-prostaglandin E1 methyl ester) the appearance of radiolabeled compounds in plasma and urine were studied in early pregnant patients. Following iv administration, ONO-802 was rapidly hydrolyzed to the free acid which disappeared from plasma with an approximate half-life of 10-15 min. About 50% of the injected amount of compound was excreted in urine during the first 24 hr after injection. The structures of 16 urinary metabolites were determined. These data demonstrated that, following hydrolysis of ONO-802 to the free acid, the latter can undergo beta- and omega-oxidation like other prostaglandin analogs where enzymatic attack of the 15-hydroxyl group has been blocked. Some of the metabolites were excreted as conjugates (sulfates, glucuronides?) and, in two, the oxo group at C-9 had been reduced to a hydroxyl. Following vaginal administration of ONO-802 (1 mg, 60 microCi) in suppository form, radioactivity corresponding to 100-200 pg/ml of ONO-802 equivalents was found in plasma. The profile of metabolites in urine was qualitatively very similar to that after iv injection of (5,6-3H2)-ONO-802. Based on the data on excretion of metabolites in urine it was calculated that 12-28% of the dose administered vaginally was resorbed into the circulation.