Effects of defibrotide after oral and parenteral administration in patients with peripheral obliterative arterial...

Defibrotide (D) a polidesoxyribonucleotidic derivative provided with fibrinolytic and antithrombotic activity has already proven effective when administered by parenteral route in patients with peripheral obliterative arterial disease (POAD). Bioavailability studies gave evidence that the drug is absorbed by 50-70% when administered orally. Thus, aim of this trial was to evaluate whether the drug might exert similar clinical and biological effects after oral/parenteral dosing in a 2:1 ratio. This was a randomized cross-over study including 17 out patients with POAD (Leriche stage II). D was administered by oral (400 mg b.i.d.) and intramuscular route (200 mg b.i.d.), both treatments lasting 15 days. In basal conditions and at the end of both treatments the following evaluations were made: (1) absolute walking distance (tread mill); (2) Doppler ultrasonographic examination (Winsor index); (3) strain-gauge plethysmography (rest flow and peak flow). In addition in the same occasions plasma samples were collected for the assessment of plasminogen (chromogenic assay) and fibrinolytic activity (fibrin plates). Defibrotide administration was followed by a significant increase in walking distance both after oral and parenteral administration [basal conditions (IRL): 232.7 +/- 23.0 meters; oral: 273.1 +/- 28.1 m; i.m.: 277.9 +/- 26.8 m, p less than 0.01 - (IRA) basal conditions: 380.1 +/- 25.6; oral: 437.1 +/- 31.5 m; i.m.: 442.5 +/- 34.0 m, p less than 0.01] and by a significant increase in peak flow (basal conditions: 9.66 +/- 1.04; oral: 10.90 +/- 0.90; i.m.: 11.12 +/- 0.98, p less than 0.05), while Winsor index and rest flow were unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)