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  • Title: Comparison of the pharmacodynamic and pharmacokinetic profiles of two low-molecular-mass heparins in rats.
    Author: Piazolo L, Harenberg J, Malsch R, Hüttner FG, Heene DL.
    Journal: Semin Thromb Hemost; 1997; 23(2):109-17. PubMed ID: 9200334.
    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, T1/2, Amax, and AUC were comparable but tPC differed. After SC injection the aIIa activities of the LMMHs exhibited comparable T1/2 and Amax but different AUC and tPC. The plasma concentrations of the LMMHs showed comparable T1/2 but certoparin exhibited a higher Amax 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.
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