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
Ishida, M.; Nakada, Y.; Horiuchi, M.; Sakamoto, F.
Arzneimittel-Forschung 48(8): 818-821
1998
ISSN/ISBN: 0004-4172 PMID: 9748709 Document Number: 494520
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 mate rabbits. The elimination 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 cntdot 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.