Albendazole failure to control resistant nematodes in lambs: Lack of effect of fasting-induced improvement on drug absorption

Autores
Alvarez, L.; Entrocasso, C.; Lifschitz, Adrian Luis; Manazza, J.; Ceballos, Laura; Borda, B.; Lanusse, Carlos Edmundo
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Enhanced plasma availability of albendazole sulphoxide (ABZSO), the active metabolite of albendazole (ABZ), has been described in feed-restricted sheep. The aim of the present work was to determine if the absorption-related pharmacokinetic changes derived from fasting animals prior to drug treatment would modify the clinical efficacy of ABZ against resistant gastrointestinal nematodes in lambs. Forty Corriedale lambs, naturally infected with resistant gastrointestinal nematodes, were divided into 4 groups. Controls were fed ad libitum and did not receive any drug treatment. Treated animals were fed ad libitum up to 30 min prior to treatment with ABZ (3.8 mg/kg) by the intraruminal route. The control (fasted) animals were not fed during the 24-hr period prior to the start of the experiment and did not receive any drug treatment. A second treated group of animals were fasted 24 hr prior to the treatment with ABZ, as previously described for the fed-treated group. Blood samples were collected over a period of 72 hr post-treatment from 6 animals in each treated group. Plasma samples were analyzed by high performance liquid chromatography. The pharmacokinetic parameters were statistically compared using parametric statistical tests. The estimation of the efficacy of the different treatments was performed by the fecal egg count reduction test (FECRT). Additionally, 4 animals randomly chosen from the control-fed and treated groups were killed 13 days post-treatment to evaluate the efficacy against different adult nematode parasites. The results were statistically compared by parametric and non-parametric tests. Significantly (P < 0.05) higher Cmax and AUC values were observed for both the ABZSO and ABZ-sulphone (ABZSO2) metabolites in the fasted compared to the fed animals. These kinetic results may be due to a fasting-induced delay in the GI transit time which increases ABZ dissolution and GI absorption. However, a poor ABZ efficacy (measured as FECRT), compatible with a high degree of nematode resistance, was obtained in both fed (48%) and fasted (49%) animals. Haemonchus contortus and Trichostrongylus colubriformis appeared as the more reluctant species with respect to ABZ treatment. The efficacy against H. contortus ranged between 37 (fed) and 54% (fasted) and against T. colubriformis between 0% (fed) and 16% (fasted). Under these experimental conditions, the fasting-induced improvement on ABZ systemic availability (>60) did not improve its activity against nematodes with a high degree of resistance. However, the data described here for a highly resistant nematode population should not discourage the use of fasting as a practical and well-proven management tool for parasite control in ruminants.
Fil: Alvarez, L.. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Entrocasso, C.. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Manazza, J.. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Ceballos, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Borda, B.. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Materia
Albendazole
Fasting
Resistant Nematodes in Sheep
Efficacy
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/83880
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/83880
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Albendazole failure to control resistant nematodes in lambs: Lack of effect of fasting-induced improvement on drug absorptionAlvarez, L.Entrocasso, C.Lifschitz, Adrian LuisManazza, J.Ceballos, LauraBorda, B.Lanusse, Carlos EdmundoAlbendazoleFastingResistant Nematodes in SheepEfficacyhttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4Enhanced plasma availability of albendazole sulphoxide (ABZSO), the active metabolite of albendazole (ABZ), has been described in feed-restricted sheep. The aim of the present work was to determine if the absorption-related pharmacokinetic changes derived from fasting animals prior to drug treatment would modify the clinical efficacy of ABZ against resistant gastrointestinal nematodes in lambs. Forty Corriedale lambs, naturally infected with resistant gastrointestinal nematodes, were divided into 4 groups. Controls were fed ad libitum and did not receive any drug treatment. Treated animals were fed ad libitum up to 30 min prior to treatment with ABZ (3.8 mg/kg) by the intraruminal route. The control (fasted) animals were not fed during the 24-hr period prior to the start of the experiment and did not receive any drug treatment. A second treated group of animals were fasted 24 hr prior to the treatment with ABZ, as previously described for the fed-treated group. Blood samples were collected over a period of 72 hr post-treatment from 6 animals in each treated group. Plasma samples were analyzed by high performance liquid chromatography. The pharmacokinetic parameters were statistically compared using parametric statistical tests. The estimation of the efficacy of the different treatments was performed by the fecal egg count reduction test (FECRT). Additionally, 4 animals randomly chosen from the control-fed and treated groups were killed 13 days post-treatment to evaluate the efficacy against different adult nematode parasites. The results were statistically compared by parametric and non-parametric tests. Significantly (P < 0.05) higher Cmax and AUC values were observed for both the ABZSO and ABZ-sulphone (ABZSO2) metabolites in the fasted compared to the fed animals. These kinetic results may be due to a fasting-induced delay in the GI transit time which increases ABZ dissolution and GI absorption. However, a poor ABZ efficacy (measured as FECRT), compatible with a high degree of nematode resistance, was obtained in both fed (48%) and fasted (49%) animals. Haemonchus contortus and Trichostrongylus colubriformis appeared as the more reluctant species with respect to ABZ treatment. The efficacy against H. contortus ranged between 37 (fed) and 54% (fasted) and against T. colubriformis between 0% (fed) and 16% (fasted). Under these experimental conditions, the fasting-induced improvement on ABZ systemic availability (>60) did not improve its activity against nematodes with a high degree of resistance. However, the data described here for a highly resistant nematode population should not discourage the use of fasting as a practical and well-proven management tool for parasite control in ruminants.Fil: Alvarez, L.. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; ArgentinaFil: Entrocasso, C.. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; ArgentinaFil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; ArgentinaFil: Manazza, J.. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; ArgentinaFil: Ceballos, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; ArgentinaFil: Borda, B.. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; ArgentinaFil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; ArgentinaAmerican Society of Parasitologists2010-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/83880Alvarez, L.; Entrocasso, C.; Lifschitz, Adrian Luis; Manazza, J.; Ceballos, Laura; et al.; Albendazole failure to control resistant nematodes in lambs: Lack of effect of fasting-induced improvement on drug absorption; American Society of Parasitologists; Journal of Parasitology; 96; 6; 12-2010; 1204-12100022-3395CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1645/GE-2524.1info:eu-repo/semantics/altIdentifier/url/https://bioone.org/journals/journal-of-parasitology/volume-96/issue-6/GE-2524.1/Albendazole-Failure-to-Control-Resistant-Nematodes-in-Lambs--Lack/10.1645/GE-2524.1.shortinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:53:23Zoai:ri.conicet.gov.ar:11336/83880instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:53:23.477CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Albendazole failure to control resistant nematodes in lambs: Lack of effect of fasting-induced improvement on drug absorption
title Albendazole failure to control resistant nematodes in lambs: Lack of effect of fasting-induced improvement on drug absorption
spellingShingle Albendazole failure to control resistant nematodes in lambs: Lack of effect of fasting-induced improvement on drug absorption
Alvarez, L.
Albendazole
Fasting
Resistant Nematodes in Sheep
Efficacy
title_short Albendazole failure to control resistant nematodes in lambs: Lack of effect of fasting-induced improvement on drug absorption
title_full Albendazole failure to control resistant nematodes in lambs: Lack of effect of fasting-induced improvement on drug absorption
title_fullStr Albendazole failure to control resistant nematodes in lambs: Lack of effect of fasting-induced improvement on drug absorption
title_full_unstemmed Albendazole failure to control resistant nematodes in lambs: Lack of effect of fasting-induced improvement on drug absorption
title_sort Albendazole failure to control resistant nematodes in lambs: Lack of effect of fasting-induced improvement on drug absorption
dc.creator.none.fl_str_mv Alvarez, L.
Entrocasso, C.
Lifschitz, Adrian Luis
Manazza, J.
Ceballos, Laura
Borda, B.
Lanusse, Carlos Edmundo
author Alvarez, L.
author_facet Alvarez, L.
Entrocasso, C.
Lifschitz, Adrian Luis
Manazza, J.
Ceballos, Laura
Borda, B.
Lanusse, Carlos Edmundo
author_role author
author2 Entrocasso, C.
Lifschitz, Adrian Luis
Manazza, J.
Ceballos, Laura
Borda, B.
Lanusse, Carlos Edmundo
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Albendazole
Fasting
Resistant Nematodes in Sheep
Efficacy
topic Albendazole
Fasting
Resistant Nematodes in Sheep
Efficacy
purl_subject.fl_str_mv https://purl.org/becyt/ford/4.3
https://purl.org/becyt/ford/4
dc.description.none.fl_txt_mv Enhanced plasma availability of albendazole sulphoxide (ABZSO), the active metabolite of albendazole (ABZ), has been described in feed-restricted sheep. The aim of the present work was to determine if the absorption-related pharmacokinetic changes derived from fasting animals prior to drug treatment would modify the clinical efficacy of ABZ against resistant gastrointestinal nematodes in lambs. Forty Corriedale lambs, naturally infected with resistant gastrointestinal nematodes, were divided into 4 groups. Controls were fed ad libitum and did not receive any drug treatment. Treated animals were fed ad libitum up to 30 min prior to treatment with ABZ (3.8 mg/kg) by the intraruminal route. The control (fasted) animals were not fed during the 24-hr period prior to the start of the experiment and did not receive any drug treatment. A second treated group of animals were fasted 24 hr prior to the treatment with ABZ, as previously described for the fed-treated group. Blood samples were collected over a period of 72 hr post-treatment from 6 animals in each treated group. Plasma samples were analyzed by high performance liquid chromatography. The pharmacokinetic parameters were statistically compared using parametric statistical tests. The estimation of the efficacy of the different treatments was performed by the fecal egg count reduction test (FECRT). Additionally, 4 animals randomly chosen from the control-fed and treated groups were killed 13 days post-treatment to evaluate the efficacy against different adult nematode parasites. The results were statistically compared by parametric and non-parametric tests. Significantly (P < 0.05) higher Cmax and AUC values were observed for both the ABZSO and ABZ-sulphone (ABZSO2) metabolites in the fasted compared to the fed animals. These kinetic results may be due to a fasting-induced delay in the GI transit time which increases ABZ dissolution and GI absorption. However, a poor ABZ efficacy (measured as FECRT), compatible with a high degree of nematode resistance, was obtained in both fed (48%) and fasted (49%) animals. Haemonchus contortus and Trichostrongylus colubriformis appeared as the more reluctant species with respect to ABZ treatment. The efficacy against H. contortus ranged between 37 (fed) and 54% (fasted) and against T. colubriformis between 0% (fed) and 16% (fasted). Under these experimental conditions, the fasting-induced improvement on ABZ systemic availability (>60) did not improve its activity against nematodes with a high degree of resistance. However, the data described here for a highly resistant nematode population should not discourage the use of fasting as a practical and well-proven management tool for parasite control in ruminants.
Fil: Alvarez, L.. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Entrocasso, C.. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Manazza, J.. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Ceballos, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Borda, B.. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
description Enhanced plasma availability of albendazole sulphoxide (ABZSO), the active metabolite of albendazole (ABZ), has been described in feed-restricted sheep. The aim of the present work was to determine if the absorption-related pharmacokinetic changes derived from fasting animals prior to drug treatment would modify the clinical efficacy of ABZ against resistant gastrointestinal nematodes in lambs. Forty Corriedale lambs, naturally infected with resistant gastrointestinal nematodes, were divided into 4 groups. Controls were fed ad libitum and did not receive any drug treatment. Treated animals were fed ad libitum up to 30 min prior to treatment with ABZ (3.8 mg/kg) by the intraruminal route. The control (fasted) animals were not fed during the 24-hr period prior to the start of the experiment and did not receive any drug treatment. A second treated group of animals were fasted 24 hr prior to the treatment with ABZ, as previously described for the fed-treated group. Blood samples were collected over a period of 72 hr post-treatment from 6 animals in each treated group. Plasma samples were analyzed by high performance liquid chromatography. The pharmacokinetic parameters were statistically compared using parametric statistical tests. The estimation of the efficacy of the different treatments was performed by the fecal egg count reduction test (FECRT). Additionally, 4 animals randomly chosen from the control-fed and treated groups were killed 13 days post-treatment to evaluate the efficacy against different adult nematode parasites. The results were statistically compared by parametric and non-parametric tests. Significantly (P < 0.05) higher Cmax and AUC values were observed for both the ABZSO and ABZ-sulphone (ABZSO2) metabolites in the fasted compared to the fed animals. These kinetic results may be due to a fasting-induced delay in the GI transit time which increases ABZ dissolution and GI absorption. However, a poor ABZ efficacy (measured as FECRT), compatible with a high degree of nematode resistance, was obtained in both fed (48%) and fasted (49%) animals. Haemonchus contortus and Trichostrongylus colubriformis appeared as the more reluctant species with respect to ABZ treatment. The efficacy against H. contortus ranged between 37 (fed) and 54% (fasted) and against T. colubriformis between 0% (fed) and 16% (fasted). Under these experimental conditions, the fasting-induced improvement on ABZ systemic availability (>60) did not improve its activity against nematodes with a high degree of resistance. However, the data described here for a highly resistant nematode population should not discourage the use of fasting as a practical and well-proven management tool for parasite control in ruminants.
publishDate 2010
dc.date.none.fl_str_mv 2010-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/83880
Alvarez, L.; Entrocasso, C.; Lifschitz, Adrian Luis; Manazza, J.; Ceballos, Laura; et al.; Albendazole failure to control resistant nematodes in lambs: Lack of effect of fasting-induced improvement on drug absorption; American Society of Parasitologists; Journal of Parasitology; 96; 6; 12-2010; 1204-1210
0022-3395
CONICET Digital
CONICET
url http://hdl.handle.net/11336/83880
identifier_str_mv Alvarez, L.; Entrocasso, C.; Lifschitz, Adrian Luis; Manazza, J.; Ceballos, Laura; et al.; Albendazole failure to control resistant nematodes in lambs: Lack of effect of fasting-induced improvement on drug absorption; American Society of Parasitologists; Journal of Parasitology; 96; 6; 12-2010; 1204-1210
0022-3395
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1645/GE-2524.1
info:eu-repo/semantics/altIdentifier/url/https://bioone.org/journals/journal-of-parasitology/volume-96/issue-6/GE-2524.1/Albendazole-Failure-to-Control-Resistant-Nematodes-in-Lambs--Lack/10.1645/GE-2524.1.short
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society of Parasitologists
publisher.none.fl_str_mv American Society of Parasitologists
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.069144

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