Pharmacokinetics of recombinant hirudin in healthy horses.
BACKGROUND
Recombinant (r)-hirudin is a specific inhibitor of thrombin that is independent of the activity of antithrombin.


OBJECTIVE
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.


CONCLUSIONS
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.
Feige
K
K
The Equine Clinic, Faculty of Veterinary Medicine, University of Zurich, Winterthurerstrasse 260, CH-8057 Zurich, Switzerland.
Dennler
M
M
Kästner
S B R
SB
Wunderli-Allenspach
H
H
Demuth
D
D
Huber
A
A
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006207:Half-Life; D006629:Hirudins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006736:Horses / Q000378:metabolism*; D007275:Injections, Intravenous / Q000662:veterinary; D007279:Injections, Subcutaneous / Q000662:veterinary; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D010314:Partial Thromboplastin Time / Q000662:veterinary
D005343:Fibrinolytic Agents; D006629:Hirudins