Tanabe K, Terada Y, Shibutani T, Kunitada S, Kondo T
Tokyo R&D Center, Daiichi Pharmaceutical Co., Ltd, Japan.
Thromb Res. 1999 Oct 15;96(2):135-43. doi: 10.1016/s0049-3848(99)00091-2.
(+)-2S-2-[4-[[(35S)-1-acetimidoyl-3-pyrrolidinyl]oxy]phenyl]-3-[7- amidino-2-napthyl]propanoic acid hydrochloride pentahydrate (DX-9065a) is an antithrombin III-independent, selective inhibitor of activated blood coagulation factor X (FXa). We investigated the protective effects of DX-9065a against tumor-bearing experimental disseminated intravascular coagulation (DIC) induced by the inoculation of AH-109A cells into rats. DX-9065a was subcutaneously administered at doses of 0.03 and 0.1 mg/kg/hour through an osmotic pump transplanted immediately after the inoculation of the tumor cells during the observation period. Platelet count decreased 12 days after the inoculation, concomitant with an increase in the thrombin-antithrombin III complex and fibrin and fibrinogen degradation products. Doses of 0.03 and 0.1 mg/kg/hour of DX-9065a significantly inhibited the decrease in plasma fibrinogen concentration and platelet count 13 days after the inoculation, respectively. These findings suggest that direct, selective inhibition of FXa by DX-9065a improves the hypercoagulable state induced by the progress of solid tumor.
（+）-2S-2-[4-[[(35S)-1-脒基亚氨基-3-吡咯烷基]氧基]苯基]-3-[7-脒基-2-萘基]丙酸盐酸盐五水合物（DX-9065a）是一种不依赖抗凝血酶III的活化凝血因子X（FXa）选择性抑制剂。我们研究了DX-9065a对将AH-109A细胞接种到大鼠体内诱导的荷瘤实验性弥散性血管内凝血（DIC）的保护作用。在观察期内，于接种肿瘤细胞后立即通过植入的渗透泵以0.03和0.1 mg/kg/小时的剂量皮下给予DX-9065a。接种后12天血小板计数下降，同时凝血酶-抗凝血酶III复合物以及纤维蛋白和纤维蛋白原降解产物增加。接种后13天，0.03和0.1 mg/kg/小时剂量的DX-9065a分别显著抑制血浆纤维蛋白原浓度和血小板计数的下降。这些发现表明，DX-9065a对FXa的直接、选择性抑制改善了实体瘤进展诱导的高凝状态。
