Study on pharmacokinetics of radioactive labelled defibrotide after oral or intravenous administration in rats.
Defibrotide (D) was labelled with 125I or with 32P. The radiolabelled compounds ([125I]-Defibrotide ([125I]-D), [32P]-Defibrotide ([32P]-D) retained the same profibrinolytic activity, in vitro, as the parent drug, suggesting that the labelling procedures had not modified the pharmacological properties of D and hence that its chemical structure was not affected significantly. After single intravenous or oral administration of [125I]-D or [32P]-D the pharmacokinetic parameters for the two labels were generally in good agreement (75%). t 1/2 alpha was in the range of minutes while t 1/2 beta was in the range of hours. Bioavailability, following single oral administration of [125I]-D or [32P]-D, was in the range of 58-70%. These data suggest that D, in spite of its macromolecular nature, is absorbed, after oral administration, fairly well.
Fisher
J
J
Inveresk Research International, Tranent, Scotland.
Holland
T K
TK
Pescador
R
R
Porta
R
R
Ferro
L
L
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D010761:Phosphorus Radioisotopes / Q000493:pharmacokinetics; D011089:Polydeoxyribonucleotides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005343:Fibrinolytic Agents; D007457:Iodine Radioisotopes; D010761:Phosphorus Radioisotopes; D011089:Polydeoxyribonucleotides; C036901:defibrotide