Import and efflux of flubendazole in Haemonchus contortus strains susceptible and resistant to anthelmintics
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
22417686
DOI
10.1016/j.vetpar.2012.02.008
PII: S0304-4017(12)00080-5
Knihovny.cz E-resources
- MeSH
- Anthelmintics metabolism pharmacokinetics pharmacology MeSH
- Haemonchus drug effects MeSH
- Drug Resistance * MeSH
- Drug Interactions MeSH
- Mebendazole analogs & derivatives metabolism pharmacokinetics pharmacology MeSH
- Organic Anion Transporters antagonists & inhibitors MeSH
- Verapamil pharmacokinetics MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Anthelmintics MeSH
- flubendazole MeSH Browser
- Mebendazole MeSH
- Organic Anion Transporters MeSH
- Verapamil MeSH
Drug entry into the body of a helminth is a key factor in the efficacy of anthelmintics. The present project was designed to study the ex vivo uptake and efflux of the benzimidazole anthelmintic flubendazole (FLU) in four strains of H. contortus: the ISE strain (fully susceptible to anthelmintics), the ISE-S strain (resistant to ivermectin), the BR strain (resistant to benzimidazoles) and the WR strain (multi-resistant). The transport of FLU between dead and living nematodes was also compared as well as the effect of verapamil, an inhibitor of the main efflux ABCB1 transporter (P-glycoprotein), on FLU accumulation in nematodes. The obtained results showed that FLU is able to effectively enter H. contortus adults due to high FLU lipophilicity. Passive diffusion is probably the only mechanism in both FLU import and efflux from nematodes. No differences in FLU transport were found among four H. contortus strains with different sensitivity to anthelmintics. No active FLU efflux from H. contortus and no effect of verapamil were observed, indicating that H. contortus cannot protect itself against FLU by the active removal of this anthelmintic from its body.
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