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Efficacy of subcutaneous doses and a new oral amorphous solid dispersion formulation of flubendazole on male jirds (Meriones unguiculatus) infected with the filarial nematode Brugia pahangi

River blindness and lymphatic filariasis are two filarial diseases that globally affect millions of people mostly in impoverished countries. Current mass drug administration programs rely on drugs that primarily target the microfilariae, which are released from adult female worms. The female worms c...

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Autores principales: Fischer, Chelsea, Ibiricu Urriza, Iosune, Bulman, Christina A., Lim, KC, Gut, Jiri, Lachau-Durand, Sophie, Engelen, Marc, Quirynen, Ludo, Tekle, Fetene, Baeten, Benny, Beerntsen, Brenda, Lustigman, Sara, Sakanari, Judy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334909/
https://www.ncbi.nlm.nih.gov/pubmed/30650084
http://dx.doi.org/10.1371/journal.pntd.0006787
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author Fischer, Chelsea
Ibiricu Urriza, Iosune
Bulman, Christina A.
Lim, KC
Gut, Jiri
Lachau-Durand, Sophie
Engelen, Marc
Quirynen, Ludo
Tekle, Fetene
Baeten, Benny
Beerntsen, Brenda
Lustigman, Sara
Sakanari, Judy
author_facet Fischer, Chelsea
Ibiricu Urriza, Iosune
Bulman, Christina A.
Lim, KC
Gut, Jiri
Lachau-Durand, Sophie
Engelen, Marc
Quirynen, Ludo
Tekle, Fetene
Baeten, Benny
Beerntsen, Brenda
Lustigman, Sara
Sakanari, Judy
author_sort Fischer, Chelsea
collection PubMed
description River blindness and lymphatic filariasis are two filarial diseases that globally affect millions of people mostly in impoverished countries. Current mass drug administration programs rely on drugs that primarily target the microfilariae, which are released from adult female worms. The female worms can live for several years, releasing millions of microfilariae throughout the course of infection. Thus, to stop transmission of infection and shorten the time to elimination of these diseases, a safe and effective drug that kills the adult stage is needed. The benzimidazole anthelmintic flubendazole (FBZ) is 100% efficacious as a macrofilaricide in experimental filarial rodent models but it must be administered subcutaneously (SC) due to its low oral bioavailability. Studies were undertaken to assess the efficacy of a new oral amorphous solid dispersion (ASD) formulation of FBZ on Brugia pahangi infected jirds (Meriones unguiculatus) and compare it to a single or multiple doses of FBZ given subcutaneously. Results showed that worm burden was not significantly decreased in animals given oral doses of ASD FBZ (0.2–15 mg/kg). Regardless, doses as low as 1.5 mg/kg caused extensive ultrastructural damage to developing embryos and microfilariae (mf). SC injections of FBZ in suspension (10 mg/kg) given for 5 days however, eliminated all worms in all animals, and a single SC injection reduced worm burden by 63% compared to the control group. In summary, oral doses of ASD formulated FBZ did not significantly reduce total worm burden but longer treatments, extended takedown times or a second dosing regimen, may decrease female fecundity and the number of mf shed by female worms.
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spelling pubmed-63349092019-01-31 Efficacy of subcutaneous doses and a new oral amorphous solid dispersion formulation of flubendazole on male jirds (Meriones unguiculatus) infected with the filarial nematode Brugia pahangi Fischer, Chelsea Ibiricu Urriza, Iosune Bulman, Christina A. Lim, KC Gut, Jiri Lachau-Durand, Sophie Engelen, Marc Quirynen, Ludo Tekle, Fetene Baeten, Benny Beerntsen, Brenda Lustigman, Sara Sakanari, Judy PLoS Negl Trop Dis Research Article River blindness and lymphatic filariasis are two filarial diseases that globally affect millions of people mostly in impoverished countries. Current mass drug administration programs rely on drugs that primarily target the microfilariae, which are released from adult female worms. The female worms can live for several years, releasing millions of microfilariae throughout the course of infection. Thus, to stop transmission of infection and shorten the time to elimination of these diseases, a safe and effective drug that kills the adult stage is needed. The benzimidazole anthelmintic flubendazole (FBZ) is 100% efficacious as a macrofilaricide in experimental filarial rodent models but it must be administered subcutaneously (SC) due to its low oral bioavailability. Studies were undertaken to assess the efficacy of a new oral amorphous solid dispersion (ASD) formulation of FBZ on Brugia pahangi infected jirds (Meriones unguiculatus) and compare it to a single or multiple doses of FBZ given subcutaneously. Results showed that worm burden was not significantly decreased in animals given oral doses of ASD FBZ (0.2–15 mg/kg). Regardless, doses as low as 1.5 mg/kg caused extensive ultrastructural damage to developing embryos and microfilariae (mf). SC injections of FBZ in suspension (10 mg/kg) given for 5 days however, eliminated all worms in all animals, and a single SC injection reduced worm burden by 63% compared to the control group. In summary, oral doses of ASD formulated FBZ did not significantly reduce total worm burden but longer treatments, extended takedown times or a second dosing regimen, may decrease female fecundity and the number of mf shed by female worms. Public Library of Science 2019-01-16 /pmc/articles/PMC6334909/ /pubmed/30650084 http://dx.doi.org/10.1371/journal.pntd.0006787 Text en © 2019 Fischer et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Fischer, Chelsea
Ibiricu Urriza, Iosune
Bulman, Christina A.
Lim, KC
Gut, Jiri
Lachau-Durand, Sophie
Engelen, Marc
Quirynen, Ludo
Tekle, Fetene
Baeten, Benny
Beerntsen, Brenda
Lustigman, Sara
Sakanari, Judy
Efficacy of subcutaneous doses and a new oral amorphous solid dispersion formulation of flubendazole on male jirds (Meriones unguiculatus) infected with the filarial nematode Brugia pahangi
title Efficacy of subcutaneous doses and a new oral amorphous solid dispersion formulation of flubendazole on male jirds (Meriones unguiculatus) infected with the filarial nematode Brugia pahangi
title_full Efficacy of subcutaneous doses and a new oral amorphous solid dispersion formulation of flubendazole on male jirds (Meriones unguiculatus) infected with the filarial nematode Brugia pahangi
title_fullStr Efficacy of subcutaneous doses and a new oral amorphous solid dispersion formulation of flubendazole on male jirds (Meriones unguiculatus) infected with the filarial nematode Brugia pahangi
title_full_unstemmed Efficacy of subcutaneous doses and a new oral amorphous solid dispersion formulation of flubendazole on male jirds (Meriones unguiculatus) infected with the filarial nematode Brugia pahangi
title_short Efficacy of subcutaneous doses and a new oral amorphous solid dispersion formulation of flubendazole on male jirds (Meriones unguiculatus) infected with the filarial nematode Brugia pahangi
title_sort efficacy of subcutaneous doses and a new oral amorphous solid dispersion formulation of flubendazole on male jirds (meriones unguiculatus) infected with the filarial nematode brugia pahangi
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334909/
https://www.ncbi.nlm.nih.gov/pubmed/30650084
http://dx.doi.org/10.1371/journal.pntd.0006787
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