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Semin Thromb Hemost 1997; 23(2): 109-117
DOI: 10.1055/s-2007-996078
Copyright © 1997 by Thieme Medical Publishers, Inc.

Comparison of the Pharmacodynamic and Pharmacokinetic Profiles of Two Low-Molecular-Mass Heparins in Rats

Lukas Piazolo, Job Harenberg, Reinhard Malsch, Franz G. Hüttner, Dieter L. Heene
  • From the 1st Department of Medicine, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
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Publication Date:
08 February 2008 (online)

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Abstract

The pharmacodynamic and pharmacokinetic properties of certoparin and dalteparin were analyzed after intravenous and subcutaneous administration. The two different LMMHs exhibited different molecular mass and in vitro activities. The aim of the present study was to show the extent to which these in vitro differences influenced the biological activity and pharmacokinetics in vivo. It was possible to measure the plasma concentrations of the LMMHs by using a competitive assay with protamine-coated latex beads.

Both LMMHs showed a biphasic aXa and aIIa activity curve after intravenous injection. Certoparin and dalteparin showed comparable aXa pharmacodynamics after IV and SC injection. By measuring the aIIa activities after IV administration of the LMMHs, T 1/2, A max, and AUC were comparable but tPC differed. After SC injection the aIIa activities of the LMMHs exhibited comparable T 1/2 and A max but different AUC and tPC. The plasma concentrations of the LMMHs showed comparable T 1/2 but certoparin exhibited a higher A max and AUC after IV and SC administration. The relative bioavailability of the aXa activity, aIIa activity, and the plasma concentrations ranged between 70 and 100%.

The differences in the aIIa pharmacodynamic and pharmacokinetic profiles of certoparin and dalteparin may be caused by the differences in the in vitro activities and the different molecular mass. Clinical relevance of the different pharmacologic profiles is only expected of the aIIa activity-related biological effects of the LMMHs.

Keywords:

Certoparin - dalteparin - LMM heparin - pharmacodynamics - pharmacokinetics