Pharmacokinetics of Defibrotide and of its profibrinolytic activity in the rabbit.

An extensive study of the pharmacokinetics and the pharmacokinetics of the profibrinolytic activity of Defibrotide (D) in the rabbit has been made. a two compartment model was used to describe D's pharmacokinetics. The parameters of drug disposition and the rate constant of release from tissues to central compartment were closely dose-dependent. The dose-response curves for elimination parameters were powers with a negative exponent indicating considerable saturation of this process. As a consequence, the T1/2, Co and AUC were also dose-dependent, as were the parameters describing the decrease in profibrinolytic activity in the blood stream.