ABSOLUTE AND COMPARATIVE SUBCUTANEOUS BIOAVAILABILITY OF ARDEPARIN SODIUM, A LOW-MOLECULAR-WEIGHT HEPARIN

Ardeparin sodium (Normiflo(R), Wyeth-Ayerst) is a low molecular weight heparin undergoing clinical evaluation as an antithrombotic agent. Th e objective of this study was to evaluate the absolute and comparative bioavailability of ardeparin following subcutaneous administration of three different formulations [two formulations of ardeparin at 10,000 anti-factor Xa (aXa) U/ml, but with different preservatives, and a 20 ,000 aXa U/ml formulation]. The study was conducted using a randomized 4-period crossover design (three subcutaneous treatments and one intr avenous treatment) in 24 healthy subjects, and the pharmacokinetics of ardeparin were characterized by plasma anti-factor IIa (aIIa) and ant i-factor Xa (aXa) activities. The mean absolute bioavailability of ard eparin based on aIIa activity ranged from 62% to 64% and the mean abso lute bioavailability based on aXa activity ranged from 88% to 97%. Bas ed on bioequivalence testing criteria, the three ardeparin formulation s were bioequivalent.