RESUMEN
beta-D xylosides have been shown to have venous antithrombotic properties after simple oral administration. Therefore, the arterial antithrombotic effect of these compounds was investigated in vivo, using the experimental thrombosis model induced by laser injury. The products tested were administered orally, 4 h before the thrombosis induction. Two beta-D xylosides were tested (LF 09-0055 and LP 05-0030), either after a simple oral administration at 50, 100, 200, and 400 mg/kg, or after repetitive oral administration at 200 mg/kg twice daily during 5 days. These compounds increased significantly the number of laser shots required to induce arterial thrombosis and decreased the number of emboli and the duration of embolization. At single-dose or repeated administrations, these xylosides did not affect diluted thrombin time in platelet-poor plasma collected after thrombosis inductions. They induced a dermatan sulfate-like activity in the plasma of treated rats, as measured by heparin cofactor II-mediated thrombin inhibition assay. These data suggest that these xylosides are potent arterial antithrombotic agents after single or repetitive oral administrations. beta-D xylosides constitute a very promising therapeutic class of orally active antithrombotic drugs.
Asunto(s)
Fibrinolíticos/administración & dosificación , Glicósidos/administración & dosificación , Trombosis/tratamiento farmacológico , Administración Oral , Animales , Modelos Animales de Enfermedad , Rayos Láser , Masculino , Ratas , Ratas WistarRESUMEN
LMWH (Fraxiparine), and NSAIDs (Aspirin, Feldene, Indocid and Profenid) injected together in doses, 1 mg/kg (Aspirin was used at 100 mg/kg), subcutaneously into rats 30 minutes before the thrombosis induction by LASER beams, increased the number of LASER beams required to induce platelet thrombus formation, decreased the number of emboli and reduced the duration of embolization, compared with control (p < or = 0.05). Of all the studied NSAIDs being injected either with LMWH or separately 30 minutes before the thrombosis stimulation by LASER only Aspirin appeared to potentiate the antithrombotic effect of Fraxiparine. Neither LMWH nor NSAIDs (except for Aspirin) at the dosages used modified aggregatory parameters compared with control. But it was observed the inhibition of platelet aggregation by the associations of Fraxiparine with Aspirin, Feldene or Profenid, tested in the whole blood 90 minutes after the drug injections.