RESUMEN

This study describes the synthesis of compound (7), a highly hydrosoluble phosphonooxymethyl prodrug of compound alpha (4). Compound (7) improved the aqueous solubility of its precursor compound (4) by 50,000 times and it is stable at neutral pH. The prodrug showed faciolicidal activity when evaluated in vitro against excysted Fasciola hepatica metacercariae. The in vivo evaluation of (7) was carried out via oral, intramuscular and subcutaneous administration in sheep artificially infected with F. hepatica metacercariae. At an intramuscular dose of 4 mg/kg, the activity of (7) was similar to that of compound alpha (4) at an oral dose of 15 mg/kg.

Asunto(s)

Antiprotozoarios/química , Bencimidazoles/química , Fascioliasis/tratamiento farmacológico , Organofosfatos/química , Administración Oral , Animales , Antiprotozoarios/farmacología , Antiprotozoarios/uso terapéutico , Bencimidazoles/farmacología , Bencimidazoles/uso terapéutico , Fasciola hepatica/efectos de los fármacos , Fascioliasis/parasitología , Fascioliasis/veterinaria , Inyecciones Intramusculares , Inyecciones Subcutáneas , Organofosfatos/farmacología , Organofosfatos/uso terapéutico , Profármacos/química , Profármacos/farmacología , Profármacos/uso terapéutico , Ovinos , Solubilidad , Agua/química