STUDY ON PHARMACOKINETICS OF RADIOACTIVE LABELED DEFIBROTIDE AFTER ORAL OR INTRAVENOUS ADMINISTRATION IN RATS

Defibrotide (D) was labelled with I-125 or with P-32. The radiolabelle d compounds ([I-125]-Defibrotide ([I-125]-D), [P-32]-Defibrotide ([P-3 2]-D) retained the same profibrinolytic activity, in vitro, as the par ent drug, suggesting that the labelling procedures had not modified th e pharmacological properties of D and hence that its chemical structur e was not affected significantly. After single intravenous or oral adm inistration of [I-125]-D or [P-32]-D the pharmacokinetic parameters fo r the two labels were generally in good agreement (75%). t1/2 alpha wa s in the range of minutes while t1/2 beta was in the range of hours. B ioavailability, following single oral administration of [I-125]-D or [ P-32]-D, was in the range of 58-70%. These data suggest that D, in spi te of its macromolecular nature, is absorbed, after oral administratio n, fairly well.