CHARACTERISTICS OF THE HEMOSTATIC ACTION OF KFA-1411, AN INHIBITOR OF COAGULATION FACTOR Xa (FXa), IN HUMANS AND VARIOUS ANIMALS
スポンサーリンク
概要
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This study examined a low-molecular-weight factor-Xa inhibitor, KFA-1411 (3-[N-(3-amidinophenyl)-N-[N-[4-[1-(1-iminoethyl)piperidin-4-yl]phenyl]carbamoylmethyl]aminomethyl]phenoxy-acetic acid monosulfonate-dihydrate). KFA-1411 selectively inhibited FXa among the serine proteases in the human blood-coagulation cascade with a Ki value of 1.73 nM,(selectivity ratio, 15000 versus its action on thrombin). The anticoagulant action of KFA-1411 in human plasma almost equaled that of the selective thrombin inhibitor, argatroban. KFA-1411 did not inhibit platelet aggregation at the concentration at which it showed an anticoagulant action. In contrast, argatroban, heparin, and low-molecular-weight heparin (LMWH ; dalteparin) inhibited thrombin-induced platelet aggregation at concentrations lower than those needed for their anticoagulant actions. The FXa-inhibiting action of KFA-1411 differed among animal species, the maximum effect being seen in humans, followed by monkeys and rabbits, with rats and mice showing about one-tenth the potency seen in humans. A species variation was also observed among the values obtained for KFA-1411 in respect of anticoagulant activity in plasma (monkeys again being closest to humans). These results indicate that KFA-1411 may exhibit antithrombotic efficacy without an unwanted platelet-related action in the future treatment of various thrombotic diseases. The experimental model of monkeys is recommended for estimation of the clinical effects and safety of KFA-1411 in humans.
- 日本トキシコロジー学会の論文
- 2003-02-28
著者
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Kojima Masami
Pharmacology Research Laboratory Research & Development Kissei Pharmaceutical Co. Ltd.
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Hara K
Pharmacology Research Laboratory Research & Development Kissei Pharmaceutical Co. Ltd.
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Matsuzawa A
Discovery Research Laboratory Research & Development Kissei Pharmaceutical Co. Ltd.
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Hara Kiyoto
Pharmacology Research Laboratory, Kissei Pharmaceutical Co., Ltd.
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Honma Toshiki
Discovery Research Laboratory, Research & Development, Kissei Pharmaceutical Co., Ltd.
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Uchida Masahiko
Discovery Research Laboratory, Research & Development, Kissei Pharmaceutical Co., Ltd.
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Akahane Satoshi
Discovery Research Laboratory, Research & Development, Kissei Pharmaceutical Co., Ltd.
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MATSUZAWA Akane
Discovery Research Laboratory, Research & Development, Kissei Pharmaceutical Co., Ltd.,
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MATSUZAWA Atsushi
Discovery Research Laboratory, Research & Development, Kissei Pharmaceutical Co., Ltd.,
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KOIZUMI Takashi
Discovery Research Laboratory, Research & Development, Kissei Pharmaceutical Co., Ltd.,
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Honma T
Discovery Research Laboratory Research & Development Kissei Pharmaceutical Co. Ltd.
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Akahane S
Discovery Research Laboratory Research & Development Kissei Pharmaceutical Co. Ltd.
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Akahane Satoshi
Department Of Discovery Research I Kissei Pharmaceutical Co. Ltd.
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Uchida Masahiko
Discovery Research Laboratory Research & Development Kissei Pharmaceutical Co. Ltd.
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Koizumi Takashi
Discovery Research Laboratory Research & Development Kissei Pharmaceutical Co. Ltd.
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Akahane Satoshi
Discovery Research Laboratory Research & Development Kissei Pharmaceutical Co. Ltd.
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