Intestinal absorption of prostaglandin F 2α, 15(S)-15-methyl prostaglandin F 2α and their methyl esters in the dog

Abstract

Radioactive prostaglandins were introduced into intact intestinal loops of dogs, and the venous blood draining from the segments was collected and analyzed for absorbed drugs and metabolites. From 8 to 18% of initial radioactivity accumulated in the blood in 60 min after (9- 3H]prostaglandin F 2α or its methyl ester were given. The compounds were extensively metabolized in the intestinal mucosa. Less than 0.3 % of the dose was recovered from the blood as intact prostaglandin F 2α when this compound was given, and up to 1.7% of the dose was found as prostaglandin F 2α following administration of prostaglandin F 2α methyl ester. A methyl group at carbon-15 of the prostaglandin molecule slowed down intestinal absorption considerably. From 0.8 to 1.2% of the radioactivity of the dose accumulated in the blood in 60 min when 14C-labelled 15(S)-15-methylprostaglandin F 2α was given. The methyl ester was absorbed more readily, and 2.4–4.7% of the dose reached the blood. In both cases, 25–50% of plasma radioactivity appeared as free acid (blood levels of 0.3–4.2% of the dose). Esterase activity was detected in mucosa and plasma; therefore, very little ester appeared in the blood. We conclude that intestinal administration of 15(S)-15-methylprostaglandin F 2α results in appreciable blood levels of intact compound. A methyl group at carbon-15 blocks the action of prostaglandin dehydrogenase, without preventing other degradative reactions of prostaglandins.