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.
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.
Ishida
M
M
Department of Drug Metabolism and Pharmacokinetics, New Drug R&D Laboratory, Kanebo Ltd., Osaka, Japan.
Nakada
Y
Y
Horiuchi
M
M
Sakamoto
F
F
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D002809:Chondroitin Sulfates / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D017985:Dalteparin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D003871:Dermatan Sulfate / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D004338:Drug Combinations; D005170:Factor X / Q000037:antagonists & inhibitors* / Q000652:urine; D006493:Heparin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D006497:Heparan Sulfate / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D011817:Rabbits
D000925:Anticoagulants; D002809:Chondroitin Sulfates; D017985:Dalteparin; D003871:Dermatan Sulfate; D004338:Drug Combinations; D005170:Factor X; D006493:Heparin; D006497:Heparan Sulfate; C035838:danaparoid