Preparation of dextran-bound recombinant hirudin and its pharmacokinetic behaviour

Biomed Biochim Acta. 1990;49(10):1103-8.

Abstract

Recombinant desulphatohirudin was bound via lysine residues to oxidized dextrans. The hirudin-dextran conjugates inhibit thrombin like free hirudin. The Ki-values are in the same range. In rabbits and rats the pharmacokinetic behaviour following i.v. administration of these conjugates was examined in comparison to that of hirudin. The hirudin-dextran conjugates were more slowly eliminated than hirudin, the distribution volumes in steady-state were significantly reduced, and, in comparison to hirudin, 5 to 15 times larger areas under the plasma concentration-time-curves were obtained.

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • Dextrans / pharmacology*
  • Fibrinolytic Agents / pharmacology*
  • Hirudins / analogs & derivatives*
  • Hirudins / pharmacology
  • Molecular Weight
  • Pharmacokinetics
  • Rabbits
  • Rats
  • Rats, Inbred Strains
  • Recombinant Proteins / pharmacology

Substances

  • Dextrans
  • Fibrinolytic Agents
  • Hirudins
  • Recombinant Proteins
  • desirudin