JAC Advance Access originally published online on August 8, 2006
Journal of Antimicrobial Chemotherapy 2006 58(4):886-890; doi:10.1093/jac/dkl329
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2-Hydroxypropyl-ß-cyclodextrin improves the effectiveness of albendazole against encapsulated larvae of Trichinella spiralis in a murine model
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
Received 13 January 2006; returned 2 May 2006; revised 11 July 2006; accepted 17 July 2006
*Corresponding author. Tel: +39-06-4990-2304; Fax: +39-06-4938-7065; E-mail: pozio{at}iss.it
Objectives: We evaluated whether the effectiveness of albendazole against encapsulated larvae increases when 2-hydroxypropyl-ß-cyclodextrin (HP-ßCD) is added to improve bioavailability.
Methods: Mice were infected with Trichinella spiralis and treated with albendazole alone, albendazole plus HP-ßCD 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-ßCD; 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-ßCD increases the bioavailability and consequently the effectiveness of albendazole against encapsulated Trichinella larvae.
Keywords: trichinellosis , treatment , bioavailability
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