Evaluation of Commercially Available Anthelminthics in Laboratory Models of Human Intestinal Nematode Infections.

Drug repurposing from veterinary to human medicine has been the main strategy to develop the four recommended human anthelminthics, albendazole, mebendazole, levamisole, and pyrantel pamoate, for the treatment of soil-transmitted helminthiasis. A systematic, head-to-head comparison of the anthelminthic activity profile of derivatives of these drugs and other anthelminthics developed in succession has not been conducted to date. We studied eight benzimidazoles, five macrocyclic lactones, tribendimidine, levamisole, and pyrantel pamoate in laboratory models of human intestinal nematode infections. studies were performed on L1 larval stage and adults, as well as , , , and L3 larvae and adults. The benzimidazoles showed pronounced differences against larval and adult stages, with low activity against larvae and the highest activity observed against adult (IC of flubendazole 1.1 μM). The macrocyclic lactones, on the other hand, revealed a higher activity on the larval stages, with the lowest IC values observed against L3 (IC values of 0.03-3 μM). studies were performed in the and mice models, with moxidectin and milbemycin oxime showing the highest activity against (ED values of 0.009 and 0.006 mg/kg, respectively) and moxidectin and abamectin being the most effective drugs against (ED values of 0.2 and 0.5 mg/kg, respectively). Laboratory models for soil-transmitted helminthiasis can assist characterizing potential drug candidates. Drugs should be evaluated against different species, and both the adult and larval stages as activities could differ considerably.