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Activity of tribendimidine and praziquantel combination therapy against the liver fluke Opisthorchis viverriniin vitro and in vivo

Published online by Cambridge University Press:  15 August 2012

J. Keiser ,
R. Adelfio ,
M. Vargas ,
P. Odermatt  and
S. Tesana
J. Keiser*
Affiliation:
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland University of Basel, CH-4003 Basel, Switzerland
R. Adelfio
Affiliation:
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland University of Basel, CH-4003 Basel, Switzerland
M. Vargas
Affiliation:
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland University of Basel, CH-4003 Basel, Switzerland
P. Odermatt
Affiliation:
University of Basel, CH-4003 Basel, Switzerland Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland
S. Tesana
Affiliation:
Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
*
*Fax: +41 61 284-8105 E-mail: jennifer.keiser@unibas.ch
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Abstract

Opisthorchiasis, caused by the liver fluke Opisthorchis viverrini, a food-borne trematode, is an important public health problem; however, only a single drug, praziquantel is available. We investigated tribendimidine–praziquantel combinations against O. viverriniin vitro and in vivo. The IC50 values of 0.16 μg/ml and 0.05 μg/ml were determined for praziquantel and tribendimidine, respectively, against adult O. viverriniin vitro. When O. viverrini was exposed to both drugs simultaneously (using a drug ratio based on the IC50 (1:3.2)) a synergistic effect was calculated (combination index (CI) at the IC50= 0.7). A similar result was observed when drug addition in vitro was spaced by the respective half-lives of the drugs (a CI of 0.78 at the IC50 for tribendimidine followed by praziquantel and a CI of 0.47 at the IC50 for praziquantel followed by tribendimidine). In vivo median-effect dose (ED50) values of 191 mg/kg and 147 mg/kg were calculated for praziquantel and tribendimidine, respectively. Low to moderate worm burden reductions (38–62%) were observed in O. viverrini infected hamsters when both drugs were administered simultaneously or on subsequent days, pointing to antagonistic effects in vivo. Further studies are necessary to understand the striking differences between the in vitro and in vivo observations using combinations of praziquantel and tribendimidine on O. viverrini.

Type
Research Papers
Information
Journal of Helminthology , Volume 87 , Issue 2 , June 2013 , pp. 252 - 256
Copyright
Copyright © Cambridge University Press 2012 

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