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JAC Advance Access published online on January 12, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki484
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received October 22, 2004
Accepted December 2, 2005

Original article

Evaluation of the efficacy of albendazole sulphoxide and praziquantel in combination on Taenia crassiceps cysts: in vitro studies

Francisca Palomares 1, Guadalupe Palencia 2, Javier R. Ambrosio 3, Alma Ortiz 2, and Helgi Jung-Cook 4 *

1 Laboratorio de Neuropsicofarmacología, Instituto Nacional de Neurología y Neurocirugía 14269, México D.F., México
2 Laboratorio de Neuroinmunología, Instituto Nacional de Neurología y Neurocirugía 14269, México D.F., México
3 Facultad de Medicina, UNAM, Departamento de Microbiología y Parasitología, México D.F., México
4 Laboratorio de Neuropsicofarmacología, Instituto Nacional de Neurología y Neurocirugía 14269, México D.F., México; Facultad de Química, UNAM, México D.F., México

* To whom correspondence should be addressed.
Helgi Jung-Cook, E-mail: helgi{at}servidor.unam.mx


  Abstract

Objectives: Praziquantel and albendazole are currently used for chemotherapeutic treatment of neurocysticercosis. Albendazole has been found to be more effective than praziquantel; however, it is well known that not all patients will show a complete resolution of cysts. Searching for more effective treatments, this study was designed to evaluate the effect of the combination of praziquantel and albendazole sulphoxide in a Taenia crassiceps in vitro model as well as the kind of interaction between both drugs.

Methods: In order to determine the concentration that produced 50% effect (EC50), T. crassiceps cysts were incubated in culture medium containing praziquantel (0.005-0.04 µg/mL), albendazole sulphoxide (0.021-0.16 µg/mL) or the combination of praziquantel and albendazole sulphoxide in a fixed-dose ratio (1 : 1). The experimental concentration (EC50Exp) of the combination was determined from the concentration-response curve constructed from the combined drug treatment. Isobolographic analyses were used to define the nature of the interaction between praziquantel and albendazole sulphoxide. Morphological and ultrastuctural alterations after different treatments over the parasite tissue were observed by light and transmission electron microscopy.

Results: The changes in ultrastructure were more marked with the praziquantel and albendazole sulphoxide combination. Also the cysticidal effect of the combination was observed earlier than that of each drug alone. When isobolographic analysis was employed, we found that the experimental EC50 value (0.042 µg/mL) was not significantly different from the theoretical EC50 value (0.035 µg/mL), which indicates an additive interaction between praziquantel and albendazole sulphoxide.

Conclusions: Our study suggests that the combination of praziquantel and albendazole sulphoxide could potentially improve the current neurocysticercosis treatment.

Keywords: neurocysticercosis; T. crassiceps; drug-drug interactions.
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