PHARMACOKINETICS OF HEPARIN AND ITS PHARMACODYNAMIC EFFECT ON PLASMA-LIPOPROTEIN LIPASE ACTIVITY AND COAGULATION IN HEALTHY HORSES

We evaluated the pharmacokinetics of IV administered sodium heparin an d the pharmacodynamic effect of heparin on lipoprotein lipase (LPL) ac tivity. Horses were allotted to 3 groups. Plasma samples were obtained from each horse before and at various times for 6 hours after heparin administration for determination of heparin concentration, LPL activi ty, and activated partial thromboplastin time (APTT). The disposition of heparin was dose dependent. The area under the plasma heparin conce ntration vs time curve (AUG) increased more than proportionally with d ose, indicating that heparin elimination was nonlinear. Total clearanc e of heparin was similar after the 40 and 80 IU/kg of body weight dosa ges, averaging 0.45 and 0.36 IU/kg/min, respectively. However, after a dministration of the 120 IU/kg dose, clearance was significantly less than that after the 40 IU/kg dose. The half-life of heparin averaged 5 3, 70, and 136 minutes after 40, 80, and 120 IU/kg, respectively, with significant differences observed between the low and high doses. In c ontrast to heparin, the area under the plasma concentration vs time cu rve for LPL activity increased less than proportionally with dose. Max imal LPL activity observed was independent of dose, averaging 4.8 mu m ol of free fatty acids/ml/h. The APPT was significantly prolonged for 120 minutes after administration of the 40 IU/kg dose. Correlation coe fficients for LPL activity vs either plasma heparin concentration or A PTT were less than 0.7, indicating that neither laboratory measure can be used to accurately predict plasma LPL activity.