Pharmacokinetics of recombinant hirudin in healthy horses

Abstract

Summary 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.;

Pharmacokinetics and thrombolytic effects of the recombinant tissue-type plasminogen activator in horses

“…For example, the coagulation inhibiting potential of heparin is due to accelerating the complex formation between antithrombin and various activated coagulation factors, among which factor Xa and thrombin are the most pivotal ones leading to a prevention of further clot formation [4,20]. In contrast, recombinant hirudin, a direct thrombin inhibitor acts independently of anti-thrombin activity and also inhibits fibrin bound thrombin [5]. The mechanism of action of plasminogen activator alteplase is advantageous in that it activates the thrombus associated plasminogen to plasmin leading to a direct induction of the fibrinolytic system [9].…”

“…Treatment of thrombosis is directed against further thrombus formation and commonly performed with unfractioned heparin [3] or low-molecular weight heparin [4]. Although recombinant hirudin, a specific thrombin inhibitor that dissolves thrombi, has been investigated experimentally [5], thrombolytic agents are not commonly employed in equine medicine.…”

Arzneimittelinteraktionen von Phenylbutazon und Phenprocoumon bei einem Warmblutpferd

“…Mit einem Wirkungseintritt ist allerdings erst nach Stunden zu rechnen (Byars et al, 1986), sodass Vollbluttransfusionen und eine Substitution der fehlenden Gerinnungsfaktoren mittels Plasmakonzentrat die Therapie lebensbedrohlicher Blutungen unterstützen (Majerns und Tollefsen, 2001). Als Alternative zu Phenprocoumon bieten sich Heparin-Derivate (Moore und Hinchcliff, 1994;Feige et al, 2003) und Hirudin (Feige et al, 2004) degli organi interni, oltre alle effusioni di sangue nelle cavità del corpo. Questo caso indica che, la somministrazione contemporanea del derivato cumarinico, phenprocoumon con fenilbutazone crea delle interazioni medicamentose che aumentano l'effetto anticoagulante del derivato di cumarina.…”