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Antimicrobial Agents and Chemotherapy, May 1999, p. 1052-1061, Vol. 43, No. 5
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Efficacies of Albendazole Sulfoxide and Albendazole Sulfone against In Vitro-Cultivated Echinococcus multilocularis Metacestodes

Katrin Ingold,1 Peter Bigler,2 Wolfgang Thormann,3 Tania Cavaliero,4 Bruno Gottstein,1 and Andrew Hemphill1,*

Institute of Parasitology,1 Department of Chemistry and Biochemistry,2 and Department of Clinical Pharmacology,3 University of Berne, Berne, and Institute of Parasitology, University of Zürich, Zürich,4 Switzerland

Received 2 December 1998/Returned for modification 20 January 1999/Accepted 10 February 1999

The metacestode stage of Echinococcus multilocularis is the causative agent of alveolar echinococcosis (AE), a parasitic disease affecting the liver, with occasional metastasis into other organs. Benzimidazole carbamate derivatives such as mebendazole and albendazole are currently used for chemotherapeutic treatment of AE. Albendazole is poorly resorbed and is metabolically converted to its main metabolite albendazole sulfoxide, which is believed to be the active component, and further to albendazole sulfone. Chemotherapy with albendazole has been shown to have a parasitostatic rather than a parasitocidal effect; it is not effective in all cases, and the recurrence rate is rather high once chemotherapy is stopped. Thus, development of new means of chemotherapy of AE is needed. This could include modifications of benzimidazoles and elucidiation of the respective biological pathways. In this study we performed in vitro drug treatment of E. multilocularis metacestodes with albendazole sulfoxide and albendazole sulfone. High-performance liquid chromatography analysis of vesicle fluids showed that the drugs were taken up rapidly by the parasite. Transmission electron microscopic investigation of parasite tissues and nuclear magnetic resonance spectroscopy of vesicle fluids demonstrated that albendazole sulfoxide and albendazole sulfone had similar effects with respect to parasite ultrastructure and changes in metabolites in vesicle fluids. This study shows that the in vitro cultivation model presented here provides an ideal first-round test system for screening of antiparasite drugs.

* Corresponding author. Mailing address: Institute of Parasitology, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland. Phone: (41) 31 6312384. Fax: (41) 31 6312622. E-mail: hemphill{at}ipa.unibe.ch.

Antimicrobial Agents and Chemotherapy, May 1999, p. 1052-1061, Vol. 43, No. 5
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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