Comparison of pharmacokinetic variables for two low-molecular-weight heparins after subcutaneous administration of a single dose to horses.

This research aimed to study the pharmacokinetic attributes and effects on clotting times after administering single doses of dalteparin and enoxaparin to horses. The study indicated that once-daily subcutaneous administration of these drugs may be useful as an anticoagulant treatment in horses.

Research Methods

• The research was conducted as a four-period crossover study comprising of 5 healthy adult horses.
• Single Subcutaneous (SC) injections of two types of low-molecular-weight heparins – dalteparin and enoxaparin were administered to the horses.
• To identify the effects and relationship with the doses, different quantities of these drugs were injected – 50 and 100 anti-Xa U/kg for dalteparin and 40 and 80 anti-Xa U/kg for enoxaparin.
• Various metrics like plasma anti-Xa activities, clotting times were measured, post administering the drugs to determine pharmacokinetic variables.
• The maximum prolongation of clotting times, both absolute and relative was calculated.
• To understand the association between the administered drugs and clotting times, correlation between plasma anti-Xa activities and clotting times was also determined.

Research Results

• Administration of both the doses of the 2 preparations was well-accepted by the horses.
• The measurement of anti-Xa activities could be successfully analyzed using a 1-compartment model.
• Difference in low-dose and high-dose treatments showed that the increase of area under plasma activity over time was significant along with the extension of the terminal half-life of the drug.
• The increase in maximum plasma activity was directly proportional, and peak plasma concentrations matched the prescribed concentrations found in human medicine.
• The activated partial thromboplastin time (aPTT) showed minimal changes, while the thrombin time (TT) showed more changes which were both dose-dependent and highly variable.
• The correlation between aPTT and plasma anti-Xa activities was feeble to moderate, while a moderate-to-strong correlation was found between TT and plasma anti-Xa activities.

Conclusions

• The pharmacokinetic attributes and anticoagulant properties of low-molecular-weight heparins in horses were found to be comparable to those observed in human studies.
• The results suggested that once-daily subcutaneous administration of dalteparin or enoxaparin can potentially be used as an effective anticoagulant treatment in horses.