Pharmacokinetics of low molecular weight heparins.

Abstract

When measured in terms of biological activities (using only markers of molecules with affinity for antithrombin III), the pharmacokinetics of low molecular weight heparins are clearly different from those of unfractionated heparin after intravenous and subcutaneous injections. The plasmatic anti-Factor Xa activity half-life, whatever the injected dose of the different low molecular weight heparins, is about two to four times longer than for unfractionated heparin while anti-Factor IIa plasmatic half-life is only slightly longer for enoxaparin than for unfractionated heparin. Preferential endothelial cell binding of high molecular weight heparin chains that possess greater anti-Factor IIa activity may partly explain these differences. When measured in terms of radioactive markers of molecules with either high or low affinity for antithrombin III, in native form or degraded after endocytosis by endothelial cells, using 99 m technetium labelled heparins in human volunteers, the pharmacokinetics in blood, urine and organs are similar whatever the heparin used (enoxaparin or unfractionated heparin). The radioactive half-life was longer than that of the biological activity. These results suggest that enoxaparin binds less than unfractionated heparin to proteins other than antithrombin III and that enoxaparin is partly eliminated in urine as active metabolites.