Sato M, Katsuki Y, Fukuhara K, Kawano H, Mizota M, Hamada Y, Kunihiro Y
Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Shizuoka, Japan.
Biol Pharm Bull. 1993 Apr;16(4):362-7. doi: 10.1248/bpb.16.362.
The effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate (EPA-E), highly purified ethyl ester of icosapentaenoic acid (EPA), on rabbit platelets were studied. In in vitro, highly purified EPA (62.5-3000 microM) suppressed the platelet aggregation induced by collagen, arachidonic acid (AA) and adenosine diphosphate (ADP). In ex vivo, a single administration of EPA-E (300 and 1000 mg/kg, p.o.) and repeated administrations (30 and 300 mg/kg/d, p.o.) for 2 weeks showed no effects on collagen-, AA- and ADP-induced platelet aggregation. Repeated administrations (30 and 300 mg/kg/d, p.o.) for 4 weeks suppressed the collagen-induced platelet aggregation, but not the AA- and ADP-induced platelet aggregation. Repeated administrations for 4 weeks also suppressed thromboxane B2 (TXB2) formation induced by collagen, but a single administration and repeated administrations for 2 weeks failed to inhibit TXB2 formation. The EPA level in the platelet phospholipids increased slightly with a single administration, and increased markedly with repeated administrations for 2 and 4 weeks. The AA level in the phospholipids showed practically no changes with a single and repeated administrations. These results suggested that highly purified EPA-E could reduce platelet aggregability by the change of the EPA level in the platelet phospholipids and should allow for a reasonable period of administration.
研究了全顺式-5,8,11,14,17-二十碳五烯酸乙酯（EPA-E，即高度纯化的二十碳五烯酸（EPA）乙酯）对兔血小板的影响。在体外，高度纯化的EPA（62.5 - 3000微摩尔）可抑制由胶原、花生四烯酸（AA）和二磷酸腺苷（ADP）诱导的血小板聚集。在体内，单次给予EPA-E（300和1000毫克/千克，口服）以及连续2周重复给药（30和300毫克/千克/天，口服）对胶原、AA和ADP诱导的血小板聚集均无影响。连续4周重复给药（30和300毫克/千克/天，口服）可抑制胶原诱导的血小板聚集，但对AA和ADP诱导的血小板聚集无抑制作用。连续4周重复给药还可抑制胶原诱导的血栓素B2（TXB2）形成，但单次给药以及连续2周重复给药均未能抑制TXB2形成。单次给药后血小板磷脂中的EPA水平略有升高，连续2周和4周重复给药后则显著升高。磷脂中的AA水平在单次给药和重复给药后几乎没有变化。这些结果表明，高度纯化的EPA-E可通过改变血小板磷脂中的EPA水平来降低血小板聚集性，且给药需要一段合理的时间。
