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Pharmacokinetics of recombinant hirudin in healthy horses

Author:
Feige, K., Dennler, M., Kästner, S.B.R., Wunderli-Allenspach, H., Demuth, D., Huber, A.
Source:
Equine veterinary journal 2004 v.36 no.2 pp. 135-141
ISSN:
0425-1644
Subject:
adverse effects, coagulation, enzyme inhibitors, half life, horses, pharmacokinetics, thrombin, thromboplastin
Abstract:
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.
Agid:
317910