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Pharmacokinetics of recombinant hirudin in healthy horses
K Feige1, M Dennler, S B R Kästner
1The Equine Clinic, Faculty of Veterinary Medicine, University of Zurich, Winterthurerstrasse 260, CH-8057 Zurich, Switzerland.
Reasons For Performing Study:
Recombinant (r)-hirudin is a specific inhibitor of thrombin that is independent of the activity of antithrombin.
Objectives:
To evaluate pharmacokinetic properties and coagulatory changes of r-hirudin in healthy horses.
Methods:
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.
Results:
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.
Conclusions:
Pharmacokinetics of r-hirudin in healthy horses were similar to those in man and other animal species.
Potential Relevance:
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.
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