Cadroy Y, Caranobe C, Bernat A, Maffrand J P, Sié P, Boneu B
Laboratoire d' Hémostase, Centre de Transfusion Sanguine, Toulouse, France.
Thromb Haemost. 1987 Aug 4;58(2):764-7.
This study reports on the anticoagulant, antithrombotic and bleeding effects of a new synthetic direct thrombin inhibitor (SDTI) in comparison with standard heparin (SH). The anticoagulant effect was determined with the thrombin clotting time (TCT) and the activated partial thromboplastin time (APTT). SDTI was more potent than SH in prolonging the TCT, but as potent as SH in prolonging the APTT. The antithrombotic effect was determined using a modified Wessler model in the rabbit, either 30 min after a continuous IV infusion of increasing doses or at various times after a single SC injection (20 mg/kg). After continuous IV infusion of 187 micrograms/kg/h of SDTI and of 60 micrograms/kg/h of SH, significant thrombus prevention effects were obtained (59 and 57% respectively). Increasing the dose of SDTI up to 3000 micrograms/kg/h did not significantly improve the antithrombotic effect. After SC injection, a significant antithrombotic effect was observed for 12 h with SDTI but for more than 24 h with SH. The bleeding effect was studied using the rabbit ear model 15 min after a continuous infusion of 7.5 and 15 mg/kg/h: the amounts of blood loss were dose-dependent and comparable for SDTI and SH. These studies also indicated that SDTI possesses a considerable shorter half-life in comparison with SH. Accordingly, the ex vivo concentrations generated after continuous IV infusion or SC injection of the same dose were higher for SH than for the SDTI.
本研究报告了一种新型合成直接凝血酶抑制剂（SDTI）与标准肝素（SH）相比的抗凝、抗血栓形成和出血效应。通过凝血酶凝血时间（TCT）和活化部分凝血活酶时间（APTT）来测定抗凝效应。在延长TCT方面，SDTI比SH更有效，但在延长APTT方面与SH效力相当。使用改良的Wessler模型在兔身上测定抗血栓形成效应，方法是在持续静脉输注递增剂量30分钟后，或在单次皮下注射（20mg/kg）后的不同时间进行。持续静脉输注187μg/kg/h的SDTI和60μg/kg/h的SH后，均获得了显著的血栓预防效果（分别为59%和57%）。将SDTI剂量增加至3000μg/kg/h并未显著改善抗血栓形成效果。皮下注射后，SDTI在12小时内观察到显著的抗血栓形成效果，而SH则超过24小时。在持续输注7.5和15mg/kg/h 15分钟后，使用兔耳模型研究出血效应：失血量呈剂量依赖性，SDTI和SH相当。这些研究还表明，与SH相比，SDTI的半衰期相当短。因此，相同剂量持续静脉输注或皮下注射后，SH产生的体外浓度高于SDTI。
