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
