Macrofilaricidal efficacy of single and repeated oral and subcutaneous doses of flubendazole in < i > Litomosoides sigmodontis < /i > infected jirds

by Marc P. H übner, Alexandra Ehrens, Marianne Koschel, Bettina Dubben, Franziska Lenz, Stefan J. Frohberger, Sabine Specht, Ludo Quirynen, Sophie Lachau-Durand, Fetene Tekle, Benny Baeten, Marc Engelen, Charles D. Mackenzie, Achim Hoerauf Flubendazole (FBZ) is highly efficacious against filarial nematodes after parenteral administration and presents a promising macrofilaricidal drug candidate for the elimination of onchocerciasis and other filariae. In the present study the efficacy of a newly developed bioavailable amorphous solid dispersion (ASD) oral formulation of FBZ was investigated in theLitomosoides sigmodontis jird model. FBZ was administered to chronically infected, microfilariae-positive jirds by single (40mg/kg), repeated (2, 6 or 15mg/kg for 5 or 10 days) oral (OR) doses or single subcutaneous (SC) injections (2 or 10mg/kg). Jirds treated with 5 SC injections at 10mg/kg served as positive controls, with untreated animals used as negative controls. After OR doses, FBZ is rapidly absorbed and cleared and the exposures increased dose proportionally. SC administered FBZ was slowly released from the injection site and plasma levels remained constant up to necropsy eight weeks after treatment end. Increasing single SC doses caused less than dose-proportional exposures. At necropsy, all animals receiving 1x or 5x 10mg/kg SC FBZ had cleared all adult worms and the 1x 2mg/kg SC treatment had reduced the adult worm burden by 98%. 10x 15mg/kg OR FBZ reduced the adult wor...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research