Oxfendazole mediates macrofilaricidal efficacy against the filarial nematode < i > Litomosoides sigmodontis in vivo < /i > and inhibits < i > Onchocerca spec < /i > . motility < i > in vitro < /i >

In this study we tested oxfendazole, an anthelmintic shown to be well tolerated in phase 1 clinical trial s.In vitro, oxfendazole exhibited modest to marginal motility inhibition of adult worms ofOnchocerca gutturosa, pre-adult worms ofOnchocerca volvulus andOnchocerca lienalis microfilariae.In vivo, five days of oral treatments provided sterile cure with up to 100% macrofilaricidal efficacy in the murineLitomosoides sigmodontis model of filariasis. In addition, 10 days of oral treatments with oxfendazole inhibited filarial embryogenesis in patentL.sigmodontis-infected jirds and subsequently led to a protracted but complete clearance of microfilaremia. The macrofilaricidal effect observedin vivo was selective, as treatment with oxfendazole of microfilariae-injected na ïve mice was ineffective. Based on pharmacokinetic analysis, the driver of efficacy is the maintenance of a minimal efficacious concentration of approximately 100 ng/ml (based on subcutaneous treatment at 25 mg/kg in mice). From animal models, the human efficacious dose is predicted to range from 1 .5 to 4.1 mg/kg. Such a dose has already been proven to be safe in phase 1 clinical trials. Oxfendazole therefore has potential to be efficacious for treatment of human filariasis without causing adverse reactions due to drug-induced microfilariae killing.
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research