Pharmacodynamics of multi-dose low molecular weight heparin in healthy horses.

This research investigated the safety and efficacy of two different dosage frequencies (once or twice daily) of low molecular weight heparin (LMWH), a blood-thinning drug, administered to healthy horses over three consecutive days.

Study Sample and Methodology

• The study was performed as a randomized cross-over trial, meaning each horse received both treatments (once and twice daily LMWH administration), with a washout period in between to avoid carryover effects.
• The sample consisted of six adult mixed breed healthy female horses (mares).
• The LMWH used was Dalteparin, given at a dose of 50 U/kg under the skin (subcutaneously), either every 12 (twice daily) or 24 hours (once daily) for three days.

Measurements and Monitoring

• Throughout the study, the horses’ blood was analyzed to measure packed cell volume (PCV), platelet count, partial thromboplastin time (PTT), and anti-thrombin (AT) activity.
• The key measurement was the blood level of anti-factor Xa, a substance that inhibits blood clotting. This was measured before and at select time points after each dose of LMWH.

Findings of the Study

• Neither once nor twice daily LMWH treatment caused changes in the horses’ PCV, platelet count, or AT activity.
• While PTT values did increase throughout the study, they did not exceed the normal reference interval, indicating no abnormal clotting function.
• When LMWH was administered twice daily, anti-factor Xa activity stayed within or above the recommended range for preventing blood clots (0.1-0.2 U/mL) for 24 hours.
• However, when LMWH was given once daily, anti-factor Xa activity dropped below this range approximately 16 hours after administration.
• The total exposure to LMWH (measured by the ‘area under the curve’ of drug concentration over time) was significantly greater after the last dose compared to the first dose, for both once and twice daily administrations. This suggests ongoing accumulation of the drug in the body over the three-day period.

Overall Conclusion

• Administering LMWH once or twice daily over three consecutive days seems safe for adult horses, as it did not induce changes in major blood parameters.
• However, to maintain anti-factor Xa activity within the desired range for preventing blood clots, it appears more effective to give LMWH twice daily rather than once daily.