Pharmacological effects of a novel recombinant hirudin, CX-397, in vivo and in vitro: comparison with recombinant hirudin variant-1, heparin, and argatroban

Thromb Haemost. 1999 Feb;81(2):250-5.

Abstract

The novel recombinant hirudin analog CX-397 was investigated with respect to its pharmacological activity and antithrombin profiles in vivo and in vitro. In three different types of thrombosis models in rats, including stasis and thrombin-induced venous, glass surface-activated arterio-venous shunt, and ferric chloride-induced arterial thrombosis models, CX-397 and rHV-1 elicited potent antithrombotic effects, where the minimum effective doses of rHV-1 tended to be higher than those of CX-397 in the arterio-venous shunt and arterial thrombosis models. The hemorrhagic risk of CX-397 in template bleeding in rats was not higher than that of rHV-1, indicating that CX-397 is superior to rHV-1 for treating the platelet-dominant type of thrombosis. However, no differences were detected between CX-397 and rHV-1 in their effects on in vitro coagulation times and thrombin-induced platelet aggregation, suggesting the possibility that some unknown mechanisms other than simple thrombin inhibition are also involved in their antithrombotic actions.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Arginine / analogs & derivatives
  • Arterial Occlusive Diseases / chemically induced
  • Arterial Occlusive Diseases / drug therapy
  • Arterial Occlusive Diseases / prevention & control*
  • Arteriovenous Shunt, Surgical
  • Chlorides
  • Drug Evaluation, Preclinical
  • Ferric Compounds / toxicity
  • Fibrinolytic Agents / pharmacology*
  • Fibrinolytic Agents / therapeutic use
  • Fibrinolytic Agents / toxicity
  • Glass
  • Hemorrhage / chemically induced
  • Heparin / pharmacology
  • Heparin / therapeutic use
  • Heparin / toxicity
  • Hirudin Therapy
  • Hirudins / analogs & derivatives*
  • Hirudins / chemistry
  • Hirudins / pharmacology
  • Hirudins / toxicity
  • Molecular Sequence Data
  • Pipecolic Acids / pharmacology
  • Pipecolic Acids / therapeutic use
  • Pipecolic Acids / toxicity
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation Inhibitors / therapeutic use
  • Platelet Aggregation Inhibitors / toxicity
  • Rats
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Recombinant Proteins / toxicity
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Serine Proteinase Inhibitors / pharmacology
  • Serine Proteinase Inhibitors / therapeutic use
  • Serine Proteinase Inhibitors / toxicity
  • Sulfonamides
  • Thrombin / antagonists & inhibitors
  • Thrombin / pharmacology
  • Thrombosis / chemically induced
  • Thrombosis / drug therapy
  • Thrombosis / prevention & control*
  • Vena Cava, Inferior
  • Venous Thrombosis / drug therapy
  • Venous Thrombosis / prevention & control*

Substances

  • CX 397
  • Chlorides
  • Ferric Compounds
  • Fibrinolytic Agents
  • Hirudins
  • Pipecolic Acids
  • Platelet Aggregation Inhibitors
  • Recombinant Proteins
  • Serine Proteinase Inhibitors
  • Sulfonamides
  • Heparin
  • Arginine
  • Thrombin
  • argatroban
  • desirudin
  • ferric chloride