Pharmacokinetics of heparin and its pharmacodynamic effect on plasma lipoprotein lipase activity and coagulation in healthy horses.

The research paper investigates how heparin, when administered intravenously, impacts the performance and presence of lipoprotein lipase in horses. It indicates that the way horses’ bodies process heparin is dependent on the dosage, affecting both its elimination and half-life. The study also reveals that neither activated partial thromboplastin time (APTT) nor plasma heparin concentration can be relied on to accurately predict plasma LPL activity.

Overview of Methodology

• Horses in the experiment were divided into three groups.
• Plasma samples were collected from each horse before and at set intervals for six hours following heparin administration. These samples were then analyzed to determine heparin concentration, lipoprotein lipase (LPL) activity, and Activated Partial Thromboplastin Time (APTT).

Heparin Dispensation and Elimination

• The study found that the manner in which heparin was dispensed in horses’ bodies relied on the dosage.
• As the dosage was increased, the Area Under the Curve (AUC) i.e., the overall exposure to heparin also increased, indicating that heparin’s elimination was nonlinear.
• Certain similarities were observed in heparin clearance after administering 40 and 80 IU/kg of body weight dosages. However, the clearance was significantly lower when the dosage was increased to 120 IU/kg.
• The half-life of heparin increased with a rise in dosage, revealing significant variations between the lowest and highest doses.

Effects on Lipoprotein Lipase (LPL) Activity

• In contrast to how heparin responded, the AUC for LPL activity didn’t increase in proportion with the increase in dosage.
• LPL activity seemed to reach a peak independent of the heparin dose, averaging a certain rate of free fatty acids release.

Effects on Activated Partial Thromboplastin Time (APTT)

• APTT was found to significantly extend for 120 minutes after administering the 40 IU/kg dose.

Limited Predictability of LPL Activity

• The correlation coefficients for LPL activity relative to either plasma heparin concentration or APTT were found to be less than 0.7.
• This indicates that neither the plasma heparin concentration nor the APTT can be relied upon to provide an accurate prediction of plasma LPL activity.