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Interactions of mefloquine with praziquantel in the Schistosoma mansoni mouse model and in vitro

Keiser, J. and Manneck, T. and Vargas, M.. (2011) Interactions of mefloquine with praziquantel in the Schistosoma mansoni mouse model and in vitro. The journal of antimicrobial chemotherapy, Vol. 66, H. 8. pp. 1791-1797.

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Official URL: http://edoc.unibas.ch/dok/A6002251

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Abstract

Objectives Mefloquine has interesting antischistosomal properties, hence it might be an attractive partner drug for combination treatment with praziquantel. The aim of this study was to evaluate activities of mefloquine/praziquantel combinations against Schistosoma mansoni in vitro and in vivo. Methods Dose-response relationships were established following exposure of adult S. mansoni to mefloquine, praziquantel and fixed dose combinations of mefloquine/praziquantel in vitro. S. mansoni-infected mice were treated orally with selected doses of single drugs and drug combinations 7 weeks post-infection. Results We calculated in vitro LC(50) values of 0.024 and 1.9 mug/mL for praziquantel and mefloquine, respectively. Mefloquine/praziquantel combinations showed synergistic effects, with combination index (CI) values >1 when adult S. mansoni were simultaneously incubated with both drugs in vitro. Reduced viabilities were also observed when schistosomes were first exposed to mefloquine followed by praziquantel in vitro. ED(50)s of 62 mg/kg and 172 mg/kg were determined for mefloquine and praziquantel against adult S. mansoni in vivo, respectively. Combinations of praziquantel (50 or 100 mg/kg) followed the next day by mefloquine (50 or 100 mg/kg) treatment revealed only moderate total worm burden reductions of 47.8%-54.7%. On the other hand, when both drugs (100 mg/kg each) were either given simultaneously or mefloquine was given prior to praziquantel, high total and female worm burden reductions of 86.0%-93.1% were observed. For the later treatment regimen, synergistic effects (CI > 1) were calculated when mefloquine and praziquantel were combined using a fixed dose ratio based on their ED(50)s. Conclusions Combinations of mefloquine and praziquantel may have clinical utility in the treatment of schistosomiasis
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)
UniBasel Contributors:Manneck, Theresia and Keiser, Jennifer
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Academic Press
ISSN:0305-7453
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Nov 2012 16:22
Deposited On:08 Nov 2012 16:12

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