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[法尼醇吲哚美辛对血液凝固的影响。与吲哚美辛在正常大鼠及华法林诱导的低凝血酶原血症大鼠中的比较]

[Influence of indometacin farnesil on blood coagulation. Comparison with indomethacin in normal rats and warfarin induced hypoprothrombinemic rats].

作者信息

Hara K, Akiyama Y, Kato Y, Orikasa E, Takahira H, Tajima T

机构信息

Department of Pharmacology, Tokyo Research Laboratories, Eisai Co., Ltd., Japan.

出版信息

Nihon Yakurigaku Zasshi. 1988 Dec;92(6):365-73. doi: 10.1254/fpj.92.365.

Abstract

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.

摘要

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。

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