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JAC Advance Access published online on August 8, 2006

Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl329
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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 January 13, 2006
Revised July 11, 2006
Accepted July 17, 2006

Brief report

2-Hydroxypropyl-{beta}-cyclodextrin improves the effectiveness of albendazole against encapsulated larvae of Trichinella spiralis in a murine model

Adriano Casulli 1, Maria Angeles Gomez Morales 1, Bruno Gallinella 2, Luciana Turchetto 2, and Edoardo Pozio 1 *

1 Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy
2 Department of Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy

* To whom correspondence should be addressed.
Edoardo Pozio, E-mail: pozio{at}iss.it


   Abstract

Objectives: We evaluated whether the effectiveness of albendazole against encapsulated larvae increases when 2-hydroxypropyl-{beta}-cyclodextrin (HP-{beta}CD) is added to improve bioavailability.

Methods: Mice were infected with Trichinella spiralis and treated with albendazole alone, albendazole plus HP-{beta}CD or not at all (controls) (Experiment I). Both immediately after treatment [76 days post-infection (p.i.)] and later (139 days p.i.) larvae were recovered, and the mean count was expressed in proportion to the larva count for controls. To evaluate the infectivity of the recovered larvae, the larvae recovered at 76 days p.i. and 139 days p.i. were used to infect another three groups (Experiments II and III, respectively).

Results: At 76 days p.i., the percentage of larvae recovered was 77.4% for mice treated with albendazole alone and 61.2% for those treated with albendazole plus HP-{beta}CD; at 139 days p.i., these percentages were 67.4% and 40.9%, respectively (Experiment I). In Experiments II and III, the percentage of larvae collected from the albendazole group and the combined-treatment group was 55.2% and 27.6%, and 53.1% and 26.6%, respectively. The ABZSO active metabolite was analysed to determine the bioavailability of albendazole. For the combined-treatment group, the area under the plasma concentration-time curve between 0 and 6 h was higher than that for the albendazole group.

Conclusions: These data suggest that HP-{beta}CD increases the bioavailability and consequently the effectiveness of albendazole against encapsulated Trichinella larvae.

Keywords: trichinellosis; treatment; bioavailability.
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