Pharmacokinetics of recombinant hirudin in healthy horses.
Authors: Feige K, Dennler M, Kästner S B R, Wunderli-Allenspach H, Demuth D, Huber A
Journal: Equine veterinary journal
Summary
Recombinant hirudin, a direct thrombin inhibitor that works independently of antithrombin, has potential application in equine thrombotic conditions, but its pharmacokinetic properties in horses had not been characterised. Feige and colleagues administered r-hirudin intravenously (0.4 mg/kg as a single bolus) to two healthy horses and subcutaneously (0.4 mg/kg every 12 hours for three days) to six healthy horses, then tracked plasma concentrations and coagulation parameters over 720 minutes and three days respectively. Following intravenous injection, elimination half-lives ranged from 58 to 80 minutes, whilst subcutaneous dosing achieved peak plasma concentrations at 128 ± 55 minutes with a longer terminal half-life of 561 ± 364 minutes; the activated partial thromboplastin time (aPTT) extended to approximately 1.9 times baseline values within 1.5 hours of administration, with no systemic or local adverse effects observed. The pharmacokinetic profile mirrors that documented in humans and other species, supporting the feasibility of using r-hirudin in clinical equine practice, though further investigation in diseased horses is essential to establish therapeutic efficacy and optimal dosing regimens for conditions such as thromboembolism or laminitis-associated coagulopathy.
Read the full abstract on PubMed
Practical Takeaways
- •R-hirudin appears safe and tolerable in healthy horses with appropriate dosing, suggesting potential for use in equine thrombotic conditions
- •Subcutaneous administration every 12 hours provides sustained anticoagulation, making it more practical than IV dosing for field conditions
- •Further efficacy studies in diseased horses are needed before clinical recommendations can be made for specific equine conditions
Key Findings
- •IV administration of r-hirudin 0.4 mg/kg resulted in elimination half-lives of 58-80 minutes in healthy horses
- •Subcutaneous administration achieved maximum plasma concentration at 128±55 minutes with terminal half-life of 561±364 minutes
- •aPTT prolongation of 1.9±0.2 times baseline occurred 1.5 hours post-administration with no systemic or local adverse effects
- •R-hirudin pharmacokinetics in horses are comparable to those in humans and other animal species