Studies on the metabolic disposition of ethyl eicosapentaenoate(EPA-E) in rats and dogs.

Abstract

Plasma level, tissue distribution and excretion of ethyl eicosapentaenoate(EPA-E) were studied after oral administration of 14C-uniformly labelled EPA-E to rats and dogs and the following results were obtained. 1. The maximum concentration of radioactivity in plasma was obtained at 6-9 hr and at 24hr after dosing in rats and dogs, respectively. The elimination of radioactivity from plasma was biphasic. 2. The radioactivity administered to rats was mainly excreted in expired air. 3. The cumulative biliary excretion of radioactivity was 2.9 % of the dose within 24 hr. 4. The concentration of radioactivity in each tissue reached maximum at 9-24hr after dosing except for brain, fat, skin, muscle and aorta in which the concentration reached maximum at 1 week and subsequently decreased gradually. The elimination rate of radioactivity from each tissue was almost as same as that from plasma or a little slower. 5. Foeto-placental transfer of radioactivity in the pregnant rats at 12 and 19 days of gestation was observed but its extent was low. 6. The milk level of radioactivty in the lactating rats reached maximum at 24 hr and was 6-14 times higher than that in the maternal blood after 24hr. 7. Radioactive substances in plasma were mainly bound to plasma protein in rats and dogs. 8. During daily repeated administration to rats, the concentration of radioactivity in plasma at 24hr after every dosing reached plateau level within the 12 days but that in each tissue increased with increase in the number of doses. No remarkable difference in elimination half-lives of radioactivity in each tissue between the single and repeated dosing was observed.