Effects of defibrotide after oral and parenteral administration in patients with peripheral obliterative arterial disease (POAD)
Craveri, A.; Tornaghi, G.; Ranieri, R.; Stanzani, M.; Landi, G.; Paganardi, L.; Passaretti, B.; Gallo, E.
International Angiology a Journal of the International Union of Angiology 9(4): 274-277
1990
ISSN/ISBN: 0392-9590 PMID: 2099963 Document Number: 351607
Defibrotide (D) a polidesoxyribonucleotidic derivative provided with fibrinolytic and antothrombotic activity has already proven effective when administered by parental 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 top 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 < 0.01 - (IRA) basal conditions: 380.1 .+-. 25.6; oral: 437.1 .+-. 31.5 m; i.m.: 442.5 .+-. 34.0 m, p < 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 < 0.05), while Winsor index and rest flow were unaffected. Plasminogen and fibrinolytic activity were also increased (plasminogen: oral: 88.8 .+-. 2.2%; i.m.: 89.2 .+-. 2.4%, p < 0.01; fibrin plates: oral: 176.6 .+-. 15.9%; i.m.: 167.4 .+-. 13.0%, p < 0.01). These data confirm that defibrotide can induce symptomatic benefit in POAD patients and improve fibrinolytic potential also after oral dosing; moreover, these dynamic results indirectly validate former bioavailability studies which suggested a 50-70% oral absorption of defibrotide.