Pharmacokinetics of heparins differing in mean molecular weight using a Xa amidolytic and Heptest clotting method.

Abstract

The pharmacokinetics of heparins ranging in mean MW from 23,000 to 4,500 were determined using a new clotting test (Heptest) and an anti-Xa, amidolytic method. No significant difference between the two methods was observed in the calculated values for distribution volume (Vd), halflife (t1/2), plasma clearance (Clp) or area under the concentration-time curve (AUC) for heparins of any MW. However, when pharmacokinetic parameters calculated from both methods were compared as a function of MW, significant differences were observed. Values for t1/2 averaged from the two methods increased with decreasing MW. The t1/2 values were 30, 35, and 50 min for the 23,000, 13,300, and 5,100 MW fractions, respectively. Similarly, AUC increased with decreasing MW while Clp decreased. All heparins were observed to have VdS approximating the plasma compartment. A slightly larger Vd was observed with the lowest MW heparin.