Pharmacokinetics of defibrotide in healthy volunteers

Haemostasis. 1986:16 Suppl 1:26-30. doi: 10.1159/000215336.

Abstract

A pharmacokinetic study of defibrotide, an antithrombotic polydeoxyribonucleotide extract, was performed in 5 healthy volunteers after rapid intravenous injection at three different doses: 0.5, 4 and 16 mg/kg. Defibrotide was given to 2 additional healthy volunteers by slow perfusion of 600 mg over 6 h, after a 200-mg intravenous bolus injection. The blood levels of defibrotide were determined by a method supplied by Crinos (detection of 6-desoxyribose). A one-compartment model was used to describe the kinetics of the drug in plasma. All the most important pharmacokinetic parameters (i.e. elimination constant, half-life, AUC and volume of distribution) were dose dependent. The half-lives were 9.8 min at 0.5 mg/kg, 14.2 min at 4 mg/kg and 21.1 min at 16 mg/kg. The dose-response curves for elimination indicated saturation. During slow infusion following the bolus injection a steady state was reached at 90-120 min, with a blood level of 10-15 micrograms/ml.

MeSH terms

  • Adult
  • Dose-Response Relationship, Drug
  • Fibrinolytic Agents / administration & dosage
  • Fibrinolytic Agents / blood*
  • Half-Life
  • Humans
  • Infusions, Parenteral
  • Injections, Intravenous
  • Kinetics
  • Male
  • Models, Biological
  • Polydeoxyribonucleotides / administration & dosage
  • Polydeoxyribonucleotides / blood*

Substances

  • Fibrinolytic Agents
  • Polydeoxyribonucleotides
  • defibrotide