Hara K, Akiyama Y, Kato Y, Orikasa E, Takahira H, Tajima T
Department of Pharmacology, Tokyo Research Laboratories, Eisai Co., Ltd., Japan.
Nihon Yakurigaku Zasshi. 1988 Dec;92(6):365-73. doi: 10.1254/fpj.92.365.
The influence of indometacin farnesil (IMF), a prodrug of indomethacin, on blood coagulation was compared with indomethacin (Ind) in normal rats and warfarin treated rats. In normal rats, 30 mg/kg of Ind very markedly shortened the extrinsic coagulation time and decreased the hematocrit, GOT, GPT and ALP in plasma at 24 hr after administration, but 3 mg/kg of Ind and both 10 and 100 mg/kg of IMF did not influence any parameter. In warfarin treated rats, 2.5 mg/kg of Ind decreased the normal prothrombin level at 48 hr, and 10 mg/kg of Ind prolonged the blood coagulation time, decreased the normal prothrombin level and hematocrit, and increased the PIVKA-II level. Moreover, at 48 hr, 3 of 6 rats in the 10 mg/kg Ind-administered group died due to intestinal bleeding. IMF at all dosages examined did not affect any of the above parameters.
将消炎痛法尼酯(IMF,消炎痛的前体药物)与消炎痛(Ind)对正常大鼠和华法林治疗大鼠血液凝固的影响进行了比较。在正常大鼠中,30mg/kg的Ind在给药后24小时非常显著地缩短了外源性凝血时间,并降低了血浆中的血细胞比容、谷草转氨酶(GOT)、谷丙转氨酶(GPT)和碱性磷酸酶(ALP),但3mg/kg的Ind以及10mg/kg和100mg/kg的IMF均未影响任何参数。在华法林治疗的大鼠中,2.5mg/kg的Ind在48小时时降低了正常凝血酶原水平,10mg/kg的Ind延长了血液凝固时间,降低了正常凝血酶原水平和血细胞比容,并提高了异常凝血酶原-II(PIVKA-II)水平。此外,在48小时时,10mg/kg Ind给药组的6只大鼠中有3只因肠道出血死亡。所有检测剂量的IMF均未影响上述任何参数。