Biochemical and pharmacologic profile of low molecular weight heparin (LU 47311, Clivarin)

Semin Thromb Hemost. 1993:19 Suppl 1:229-40.

Abstract

1. Clivarin is a homogeneous LMWH as determined by the data obtained in molecular profiling studies. 2. The limited biochemical studies carried out indicated that this LMWH has a specific potency of 124 anti-Xa IU/mg and a weaker APTT activity of approximately 30 U/mg. 3. Assay-dependent neutralization of the in vitro effects of Clivarin was noted. Protamine preparations at equigravimetric concentrations effectively neutralized the APTT and TT effects; however, Heptest and anti-Xa effects were only partially neutralized. In contrast, heparin's effects were completely neutralized by this agent. 4. PF 4 only partially neutralized the effects of Clivarin. Assay-dependent variations were noted in this study. 5. In comparison to heparin, the hemorrhagic effects of Clivarin were much weaker. 6. Clivarin produced a dosage-dependent antithrombotic action in both the intravenous and subcutaneous studies. This agent also showed sustained activity and better bioavailability characteristics than heparin. 7. Clivarin exhibited a distinct biochemical and pharmacologic profile that may be useful in the optimization of this agent.

MeSH terms

  • Animals
  • Bleeding Time
  • Hemorrhage / chemically induced
  • Heparin, Low-Molecular-Weight / antagonists & inhibitors
  • Heparin, Low-Molecular-Weight / chemistry*
  • Heparin, Low-Molecular-Weight / pharmacology
  • Humans
  • Male
  • Molecular Weight
  • Platelet Activation / drug effects
  • Platelet Factor 4 / pharmacology
  • Protamines / pharmacology
  • Protease Inhibitors / pharmacology
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley
  • Reference Standards
  • Reference Values
  • Thrombocytopenia / chemically induced
  • Thrombocytopenia / drug therapy

Substances

  • Heparin, Low-Molecular-Weight
  • Protamines
  • Protease Inhibitors
  • Platelet Factor 4
  • reviparin