Treatment of Neurocysticercosis with Flubendazole *

The antihelmintic flubendazole inhibits microtubule function through a mechanism distinct from Vinca alkaloids and displays preclinical activity in leukemia and myeloma

“…10 In humans, doses of 40 to 50 mg/kg/d for 10 days have been administered for the treatment of neurocysticercosis, and no toxicity from the drug was reported. 9 Likewise, patients received up to 50 mg/kg/d of flubendazole for up to 24 months for the treatment of alveolar echinococcosis without adverse effect. 8 The pharmacokinetics of flubendazole are also well characterized.…”

“…In these studies, patients have received up to 50 mg/kg orally daily for 24 months without serious adverse effects. [7][8][9] Healthy volunteers have also received single oral doses up to 2000 mg without toxicity. 10 In mice receiving a single dose of 5 mg/kg flubendazole, a maximal concentration (C max ) of 1.12 g/mL (3.6M) and an area under the curve (AUC) of 2.17 g/hour per milliliter with no evidence of toxicity was recorded.…”

Progress and challenges in the discovery of macrofilaricidal drugs

“…Parenteral administration of flubendazole in animal models of filariasis has not been associated with neurotoxicity and a toxicity study reported no such effects in mice given 200 mg/kg flubendazole by intraperitoneal injection daily for 14 days [59]. In addition, the fact that flubendazole has been reported to have activity against human neurocysticercosis (40 mg/kg per day for 10 days in two divided doses) without evidence of such neurotoxicity [61] suggests that systemic exposure to this drug per se is not the cause of effects seen with UMF-078. However, it should also be noted that the LD 50 of flubendazole in mice has been reported to be 200-500 mg/kg, and some neurotoxicity was observed [103].…”

“…However, no data are available to suggest that any would present therapeutic or pharmaceutical advantages over flubendazole as a macrofilaricide. As noted previously, high-dose, prolonged therapy with albendazole [53], and also flubendazole [61] and oxfendazole ( Figure 5) [62], can be used to control at least some tissue helminths; whether either is macrofilaricidal in similar regimens has not been fully evaluated. In this regard, it should be emphasized that the MDA programs associated with LF elimination strategies could generate relevant data on macrofilaricidal effects of albendazole in combination with DEC or IVM if field results were analyzed appropriately.…”

Management of Neurocysticercosis

“…Other drugs, such as metrifonate and fl ubendazole have been eventually tried in this condition but their use has been promptly abandoned due to side effects or lack of effi cacy (Salazar and Gonzalez 1972 ;Téllez-Girón et al 1984 ). Oxfendazole, a benzimidazole molecule with a long half-life, has been shown to cause a signifi cant clearance of muscle and brain cysts in swine after a single-dose trial ); this drug is now undergoing Phase I studies in humans, and if found safe, it may provide a new therapeutic alternative to albendazole or praziquantel.…”