In vitro and in vivo efficacy of tribendimidine and its metabolites alone and in combination against the hookworms Heligmosomoides bakeri and Ancylostoma ceylanicum

Worldwide, 3 billion people are at risk of hookworm infection, particularly in resource-poor countries. While control of soil-transmitted helminthiases relies mostly on chemotherapy, only few drugs are available and concern about potential emergence of drug resistance is rising. In the present study, tribendimidine, a derivative of amidantel, and its metabolites deacylated amidantel (dADT) and acetylated deacylated amidantel (AdADT) were tested in vitro and in vivo against Heligmosomoides bakeri and Ancylostoma ceylanicum, two hookworm rodent models, alone or in combination with standard drugs. Tribendimidine achieved IC(50)s88mug/ml). In vivo at single oral doses of 10mg/kg, dADT showed a slightly higher efficacy than tribendimidine, achieving worm burden reductions of 87.4% and 74.8%, respectively. At the same dose, AdADT reduced the worm burden by 57.9%. Synergistic interactions were observed with tribendimidine-levamisole combinations against A. ceylanicum in vitro (combination index at IC(50)=0.5), and in vivo (combination index at ED(90)=0.19). In conclusion, tribendimidine and dADT show potent anti-hookworm properties. The potential of the promising tribendimidine-levamisole combination should be investigated in greater detail