Comparison of the pharmacokinetics of enoxaparin (Clexane) and unfractionated heparin

Abstract

The pharmacokinetics of enoxaparin (Clexane) and unfractionated heparin were compared by crossover study in healthy volunteers, using three different assays. After intravenous administration, unfractionated heparin was cleared with a half-life of 35 min, irrespective of assay methods. However, the concentration of enoxaparin, measured by competitive binding assay, declined with the longer half-life of 60 min, and its anti-Factor IIa and anti-Factor Xa activities had half-lives of 40 and 275 min, respectively. These data may reflect more rapid clearance of longer chain molecules with anti-Factor IIa activity, or release by enoxaparin of an endogenous compound with anti-Factor Xa activity. Following subcutaneous injection, the bioavailability of enoxaparin was 3-fold greater than that of unfractionated heparin; unlike unfractionated heparin, enoxaparin was almost completely absorbed. Peak plasma concentrations occurred 3 h after injection. The pharmacokinetic parameters of enoxaparin were not affected by dose; by contrast, the half-life of unfractionated heparin was highly dose-dependent. The pharmacokinetics of both unfractionated heparin and enoxaparin did not display circadian variation, and neither preparation crossed the human placenta.