Pharmacokinetics of recombinant hirudin in healthy horses.
Abstract: 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.
Publication Date: 2004-03-25 PubMed ID: 15038436DOI: 10.2746/0425164044868666Google Scholar: Lookup
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- Journal Article
Summary
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This research study investigates the physical effects of a substance called recombinant hirudin on healthy horses, including how the body absorbs, distributes, metabolizes, and excretes it. The findings suggest that recombinant hirudin can be safely used in horses, with further studies required for its use in treating diseased horses.
Research Objective and Methodology
- The primary objective of this study was to understand how recombinant hirudin behaves in the bodies of healthy horses, specifically its pharmacokinetics and coagulatory changes.
- Eight horses were used for the study; two received a single intravenous dose of recombinant hirudin, while six received the same dose subcutaneously every 12 hours over a period of three days.
- The researchers monitored coagulation times and plasma concentration of recombinant hirudin after both intravenous and subcutaneous administration, over 720 minutes for the former and three days for the latter.
Findings and Interpretation
- No systemic or local side effects were observed in any of the horses treated with recombinant hirudin.
- Post intravenous injection, the two horses showed an elimination half-life of recombinant hirudin, which varied between 58 and 80 minutes. This means that it took this long for half of the substance to be removed from the body.
- After subcutaneous administration, the maximal plasma concentration of the substance was found an average of 128 minutes following administration, while the average terminal half-life was notably longer, at 561 minutes.
- The maximum response in terms of activated partial thromboplastin time, a measure of blood clotting, occurred roughly 1.5 hours after administration. A 1.9 fold lengthening as compared to pretreatment measures was noted.
Conclusion and Future Research
- The study concluded that the physical responses to and behaviors of recombinant hirudin in healthy horses closely mirrored those seen in humans and other animal species, implying its potential as a therapeutic agent in equine medicine.
- While the results were promising, the researchers recommend further studies to determine its effectiveness in horses with diseases, before recombinant hirudin can be officially recommended as a treatment option.
Cite This Article
APA
Feige K, Dennler M, Kästner SB, Wunderli-Allenspach H, Demuth D, Huber A.
(2004).
Pharmacokinetics of recombinant hirudin in healthy horses.
Equine Vet J, 36(2), 135-141.
https://doi.org/10.2746/0425164044868666 Publication
Researcher Affiliations
- The Equine Clinic, Faculty of Veterinary Medicine, University of Zurich, Winterthurerstrasse 260, CH-8057 Zurich, Switzerland.
MeSH Terms
- Animals
- Blood Coagulation / drug effects
- Female
- Fibrinolytic Agents / administration & dosage
- Fibrinolytic Agents / adverse effects
- Fibrinolytic Agents / pharmacokinetics
- Half-Life
- Hirudins / administration & dosage
- Hirudins / adverse effects
- Hirudins / pharmacokinetics
- Horses / metabolism
- Injections, Intravenous / veterinary
- Injections, Subcutaneous / veterinary
- Male
- Metabolic Clearance Rate / drug effects
- Partial Thromboplastin Time / veterinary
Citations
This article has been cited 1 times.- Bäumer W, Herrling GM, Feige K. Pharmacokinetics and thrombolytic effects of the recombinant tissue-type plasminogen activator in horses.. BMC Vet Res 2013 Aug 9;9:158.
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