Pharmacokinetics of defibrotide in healthy volunteers.
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.
D000328:Adult; D004305:Dose-Response Relationship, Drug; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000097:blood*; D006207:Half-Life; D006801:Humans; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D011089:Polydeoxyribonucleotides / Q000008:administration & dosage / Q000097:blood*
D005343:Fibrinolytic Agents; D011089:Polydeoxyribonucleotides; C036901:defibrotide