Feige K, Dennler M, Kästner S B R, Wunderli-Allenspach H, Demuth D, Huber A
The Equine Clinic, Faculty of Veterinary Medicine, University of Zurich, Winterthurerstrasse 260, CH-8057 Zurich, Switzerland.
Equine Vet J. 2004 Mar;36(2):135-41. doi: 10.2746/0425164044868666.
Recombinant (r)-hirudin is a specific inhibitor of thrombin that is independent of the activity of antithrombin.
To evaluate pharmacokinetic properties and coagulatory changes of r-hirudin in healthy horses.
Two clinically healthy horses received a single i.v. bolus of 0.4 mg/kg bwt r-hirudin and 6 clinically healthy horses received the same dose subcutaneously (subcut.) q. 12 h for 3 days. Coagulation times and r-hirudin plasma concentration were determined over 720 mins and 3 days after i.v. and subcut. administration, respectively.
In all horses, treatment with r-hirudin was not associated with systemic or local side effects. After i.v. injection, the 2 horses showed an elimination half-life of 58 and 80 mins, respectively. After subcut. administration, maximum plasma concentration of r-hirudin occurred at 128 +/- 55 mins and declined with a terminal half-life of 561 +/- 364 mins. Maximum response of activated partial thromboplastin time (aPTT) occurred 1.5 h after administration of r-hirudin. A prolongation of 1.9 +/- 0.2 times the pretreatment value was noted.
Pharmacokinetics of r-hirudin in healthy horses were similar to those in man and other animal species.
The results of this study indicate that r-hirudin can be used in horses, but further studies should be performed in order to prove its effectiveness in diseased horses.
重组水蛭素是一种凝血酶特异性抑制剂，其作用独立于抗凝血酶的活性。
评估重组水蛭素在健康马匹中的药代动力学特性及凝血变化。
2匹临床健康的马静脉注射一次0.4mg/kg体重的重组水蛭素，6匹临床健康的马皮下注射相同剂量，每12小时一次，共3天。分别在静脉注射和皮下注射后720分钟及3天内测定凝血时间和重组水蛭素血浆浓度。
所有马匹使用重组水蛭素治疗均未出现全身或局部副作用。静脉注射后，2匹马的消除半衰期分别为58分钟和80分钟。皮下注射后，重组水蛭素血浆浓度在128±55分钟时达到峰值，并以561±364分钟的终末半衰期下降。活化部分凝血活酶时间（aPTT）在注射重组水蛭素后1.5小时出现最大反应。观察到延长至预处理值的1.9±0.2倍。
重组水蛭素在健康马匹中的药代动力学与人及其他动物相似。
本研究结果表明重组水蛭素可用于马匹，但需进一步研究以证实其在患病马匹中的有效性。
