Pharmacokinetics of danaparoid sodium, dalteparin sodium and heparin determined by inhibitory effect on the activated coagulation factor X activity after single intravenous administration in rabbits

Abstract

The inhibitory effect on the activated coagulation factor X activity (anti-Xa activity) in plasma and urine of danaparoid sodium (DAS, CAS 9005-49-6) was compared with that of dalteparin sodium (DLS, CAS 9041-08-1) and heparin (CAS 9005-49-6) after single intravenous administration at a dose of 640 anti-Xa U/kg to male rabbits. The elimination of half-life of DAS was 9.90 h and was 6.0 times longer than that of DLS and 16.5 times longer than that of heparin. The area under the plasma concentration-time curve (AUC) of DAS was 47.13 +/- 14.55 anti-Xa U.h/ml and was 2.4 times larger than that of DLS and 2.9 times larger than that of heparin. The urinary cumulative excretion of anti-Xa activity of DAS and DLS was 42.6 +/- 6.4% and 16.4 +/- 0.8% of dose, respectively, in 24 h after dosing, respectively. But the anti-Xa activity in urine was not detected at any sampling points after administration of heparin. DAS has a longer elimination half-life and a higher renal excretion of anti-Xa activity than that of DLS and heparin. Therefore, in comparison to DLS and heparin, it seems that the anticoagulant activity of DAS has a long duration.