Synergistic interaction between praziquantel and oxfendazole or fenbendazole in a murine cysticercosis model

Up to date, the pharmacological treatment for active neurocysticercosis (NCC) includes only two drugs, praziquantel and albendazole; however, the clinical response is not always successful, due to its low bioavailability; therefore, new approaches are needed. The aim of the present study was to evaluate the pharmacological interaction between praziquantel (PZQ) and oxfendazole (OXF) in vitro; also, the drug-drug interaction between PZQ and OXF or fenbendazole (FBZ) in vivo using Taenia crassiceps metacestode was assessed. For the in vitro study, the surface of synergistic interaction (SSI) analysis was used to determine the kind of drug interaction between PZQ and OXF. Additionally, morphological and ultrastructural effects were investigated using transmission scanning electron microscopy. For the in vivo study, different doses of PZQ and FBZ or OXF were combined, and the cysticidal effect was determined. In vitro, results showed that 12 combinations exhibited synergism, and four exhibited additive effects. The 1:5 ratio of PZQ and OXF exhibited the highest synergistic effect, with an 11-fold increase in comparison to their theoretical sum. Microscopic observations revealed damage to the tegument and germinal layer; microtriches, flame cells, and muscular fibers were also affected. In vivo, results showed that PZQ + FBZ and PZQ + OXF (ratios 1:4 and 1:1, respectively) exhibited a synergistic reduction of the parasites. The findings of the present study show the potential of these combinations as a pharmacological alternative for cysticercosis treatment. Complementary studies are needed to determine their benefits in the clinical field.