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Combination chemotherapy against Clonorchis sinensis : experiments with artemether, artesunate, OZ78, praziquantel, and tribendimidine in the rat model

Keiser, Jennifer and Xiao, Shu-Hua and Smith, Thomas A. and Utzinger, Jürg. (2009) Combination chemotherapy against Clonorchis sinensis : experiments with artemether, artesunate, OZ78, praziquantel, and tribendimidine in the rat model. Antimicrobial agents and chemotherapy, Vol. 53, H. 9. S. 3770-3776.

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Official URL: http://edoc.unibas.ch/dok/A5843170

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Abstract

Caused by the Chinese liver fluke Clonorchis sinensis, clonorchiasis is of growing public health importance. Treatment and control of the disease relies on a single drug - praziquantel - and little information is available regarding combination chemotherapy. Here, we evaluated the in vivo efficacy of praziquantel combined with artemether, artesunate, OZ78, and tribendimidine, as well as an artesunate-tribendimidine combination against C. sinensis in the rat model. Data from previous experiments were included and negative binomial regression analyses were carried out to determine dose-response relationships and to study the effect of drug combination. All drugs given in monotherapy were efficacious in killing the worms; doses of 16 and 70 mg/kg of artesunate, for example, reduced worm burden by 50% and 95%, respectively. Artemether and OZ78 (12.5-50 mg/kg) showed dose-dependent killing, but no significant drug interactions when given with 150 mg/kg praziquantel, suggesting independent additive effects. In contrast, artesunate and tribendimidine (12.5-50 mg/kg) showed synergistic interactions with 150 mg/kg praziquantel. When low doses of 3.1 and 6.25 mg/kg OZ78 and artemether, respectively were combined with praziquantel (150 mg/kg) an increased worm survival - above the level observed with praziquantel monotherapy - was noted. A similar antagonism was seen when praziquantel (75 mg/kg) was combined with several of the companion drugs at varying doses. In conclusion, in vivo efficacy of praziquantel, the artemisinins, OZ78, and tribendimidine against C. sinensis is confirmed, and combination chemotherapy with praziquantel produces synergistic and antagonistic effects depending on the doses administered. Further preclinical investigations are warranted
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Helminth Drug Development (Keiser)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Eco System Health Sciences > Health Impact Assessment (Utzinger)
UniBasel Contributors:Utzinger, Jürg and Smith, Thomas A. and Keiser, Jennifer
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:American Society for Microbiology
ISSN:0066-4804
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Mar 2013 11:11
Deposited On:14 Sep 2012 06:46

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