Pharmacological properties of CY 216 and of its ACLM and BCLM components in the rabbit

Thromb Haemost. 1994 Aug;72(2):268-74.

Abstract

This study compares some in vivo pharmacological properties of CY 216 and of its ACLM and BCLM components having a molecular weight above and below 5.4 kDa respectively. The anti-factor Xa/antithrombin ratio of these compounds determined in a rabbit plasma system were 2.5 and 1.2 for CY 216 and ACLM respectively while BCLM was devoid of anti-thrombin effect. After bolus intravenous injection, continous infusion and subcutaneous administration, the clearances of anti-factor Xa activity generated by ACLM were, on the average, 2 and 1.5 times higher than those generated by BCLM and CY 216 respectively. The clearances of the anti-thrombin activity were comparable for CY216 and ACLM, and higher than those of the antifactor Xa activity. The duration of the antithrombotic effect was investigated in the Wessler model after a single subcutaneous injection of 1000 anti-factor Xa units of one of the compounds. Using thromboplastin as thrombogenic stimulus, the most efficient agent was ACLM and the antithrombotic activity was essentially correlated to the circulating anti-thrombin activity. Using human serum as thrombogenic stimulus, ACLM and BCLM were more efficient than CY 216 and the antithrombotic activity was mainly correlated to the anti-factor Xa activity. The ability of the 3 compounds to inhibit venous thrombosis growth was compared: they were found equipotent and the antithrombotic effect was independent of the anti-thrombin activity. The prohaemorrhagic properties were compared in the rabbit ear model. The activity of the 3 compounds were comparable and significantly less prohaemorrhagic than unfractionated heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Factor Xa Inhibitors
  • Hemorrhage / chemically induced
  • Infusions, Intravenous
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Molecular Weight
  • Nadroparin / administration & dosage
  • Nadroparin / chemistry
  • Nadroparin / pharmacokinetics
  • Nadroparin / pharmacology*
  • Nadroparin / toxicity
  • Rabbits
  • Thrombin / antagonists & inhibitors
  • Thrombophlebitis / pathology
  • Thrombophlebitis / prevention & control
  • Time Factors

Substances

  • Factor Xa Inhibitors
  • Nadroparin
  • Thrombin