Absorption through the peritoneum of the macromolecular profibrinolytic drug defibrotide in the rabbit.
Defibrotide is the sodium salt of a polydeoxyribonucleotide extracted from mammalian lungs by controlled depolymerization. This macromolecular compound (mean molecular weight 20,000 d) has profibrinolytic activity. It also is antithrombotic after both intravenous and oral administration. The purpose of this study was to see whether defibrotide could activate the fibrinolytic system after intraperitoneal administration, because it has been observed that in ascitic patients treated intraperitoneally with defibrotide, no occlusion of the peritoneal-jugular catheter valve draining the ascitic fluid (according to LeVeen et al.) occurred. The profibrinolytic activity of defibrotide and its plasma levels were dose dependent, with a statistically significant correlation between the fibrinolytic activities and the AUC of the plasma levels of defibrotide. No rebound effect was observed during the duration of the experiments (24 hours). We hypothesize that the fibrinolytic activity elicited by defibrotide prevented the deposition of fibrin in the catheter valve, enabling normal drainage of the ascitic fluid. The lack of rebound makes defibrotide a safe drug. The mechanism by which this macromolecular compound is absorbed is still unknown.
Porta
R
R
Crinos Biological Research Laboratories, Villa Guardia (Como), Italy.
Calvani
A B
AB
Pescador
R
R
Mantovani
M
M
Prino
G
G
D000818:Animals; D005343:Fibrinolytic Agents / Q000493:pharmacokinetics*; D008297:Male; D010537:Peritoneum; D011089:Polydeoxyribonucleotides / Q000493:pharmacokinetics*; D011817:Rabbits
D005343:Fibrinolytic Agents; D011089:Polydeoxyribonucleotides; C036901:defibrotide