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• W2034863939 abstract "1 The antithrombotic action of argatroban, a synthetic thrombin inhibitor, was studied in three models of thrombosis in the rat, and in the tail transection bleeding time test. Heparin was studied as a reference anticoagulant. 2 In the model of venous thrombosis induced by thromboplastin followed by stasis of the abdominal vena cava, argatroban had an ED50 of 125 μg kg−1, when administered as an i.v. bolus 5 min prior to the thromboplastin injection: the ED50 of heparin was 42 μg kg−1, where ED50 is the dose which reduces the weight of the thrombus by 50% compared with that of the control animals. When the two compounds were administered by continuous i.v. infusion, argatroban (ED50= 1.5 μg kg1 min−1) had the same potency as heparin (ED50= 1.2 μg kg1 min1). 3 Argatroban was active in the arterio-venous shunt model with an ED50 of 0.6mg kg−1 when the compound was given as a bolus. The ED50 of herapin was 0.04 mg kg−1 under the same conditions. The two compounds had ED50 values of 6 μg kg1 min−1(argatroban) and 3 μg kg1 min−1(heparin), when administered by continuous i.v. infusion. 4 When tested against occlusive arterial thrombus formation by electrical stimulation of the left carotid artery, both compounds given as either an i.v. bolus or a continuous infusion led to dose-dependent increases in the duration of post-lesion vessel patency. Heparin bolus was more active than argatroban on a weight basis, in that 2mg kg−1 gave a similar increase in the time to occlusion as 8mg kg−1argatroban. As in the other models, when given as continuous infusions, argatroban (111% increase in time to occlusion at 20 μg kg−1, min−1) had similar activity to that of heparin (180% increase at 25 μg kg−1 min−1) on a weight basis. Hoever, the antithrombotic effects of argatroban were accompanied by only moderate changes in the coagulation parameters (thrombin time and activated partial thromboplastin time, APTT), whereas, even at a subthreshold dose of heparin (12.5 μg kg−1 min−1), both the thrombin time and the APTT were greater than 150 s. 5 Infusions of both compounds caused dose-dependent increases in the tail transection bleeding time, with the dose of argatroban that doubles the bleeding time (11 μg kg−1 min−1) being five times greater than that of heparin (ED100= 2.2 μg kg−1 min−1). 6 These data show that, when administered as an intravenous infusion, argatroban is a potent antithrombotic agent in rat models of venous ‘mixed’ and arterial thrombosis, this effect can be obtained with a lower degree of systemic anticoagulation than with heparin in the arterial model, and argatroban has a lower haemorrhagic potential than that of heparin." @default.
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• W2034863939 date "1994-12-01" @default.
• W2034863939 modified "2023-10-16" @default.
• W2034863939 title "Antithrombotic actions of argatroban in rat models of venous, ‘mixed’ and arterial thrombosis, and its effects on the tail transection bleeding time" @default.
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• W2034863939 doi "https://doi.org/10.1111/j.1476-5381.1994.tb17126.x" @default.
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