EFFECTS OF HIGHLY PURIFIED ETHYL ALL-CIS-5,8,11,14,17-ICOSAPENTAENOATE (EPA-E) ON RABBIT PLATELETS

The effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate (EPA-E), hi ghly purified ethyl ester of icosapentaenoic acid (EPA), on rabbit pla telets were studied. In in vitro, highly purified EPA (62.5-3000 mum) suppressed the platelet aggregation induced by collagen, arachidonic a cid (AA) and adenosine diphosphate (ADP). In ex vivo, a single adminis tration of EPA-E (300 and 1000 mg/kg, p.o.) and repeated administratio ns (30 and 300 mg/kg/d, p.o.) for 2 weeks showed no effects on collage n-, AA- and ADP-induced platelet aggregation. Repeated administrations (30 and 300 mg/kg/d, p.o.) for 4 weeks suppressed the collagen-induce d platelet aggregation, but not the AA- and ADP-induced platelet aggre gation. Repeated administrations for 4 weeks also suppressed thromboxa ne B2 (TXB2) formation induced by collagen, but a single administratio n and repeated administrations for 2 weeks failed to inhibit TXB2 form ation. The EPA level in the platelet phospholipids increased slightly with a single administration, and increased markedly with repeated adm inistrations for 2 and 4 weeks. The AA level in the phospholipids show ed practically no changes with a single and repeated administrations. These results suggested that highly purified EPA-E could reduce platel et aggregability by the change of the EPA level in the platelet phosph olipids and should allow for a reasonable period of administration.