Modulation of metabolic and transport processes: a valuable tool for improving anthelmintic efficacy?

Autores
Viviani, Paula; Virkel, Guillermo Leon; Luque, Sonia Elisabet; Lloberas, Maria Mercedes; Lanusse, Carlos Edmundo; Lifschitz, Adrian Luis
Año de publicación
2018
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
In vivo modulation of drug metabolizing enzymes and transporters may delay the elimination and enhance the systemic availability of anthelmintic compounds. Parasite exposure to the active molecules can be enhanced through their combination with transport modulators or other active anthelmintics. However, the practical relevance of such interactions is unknown. This work aims at assessing the occurrence of PK/PD interactions between (a) oxfendazole and triclabendazole; (b) moxidectin and loperamide; and (c) abamectin and ivermectin/itraconazole in lambs.Materials and MethodsLambs parasitized with nematodes highly resistant to benzimidazole and macrocyclic lactones were used.Experiment 1: Lambs (three groups, n=7 each) were treated with oxfendazole (5 mg/kg PO), triclabendazole (12 mg/kg PO) or their combination;Experiment 2: Lambs (two groups, n=7 each) were treated with moxidectin (0.2 mg/kg SC) alone or in combination with loperamide (0.16 mg/kg PO) and pluronic 123;Experiment 3: Lambs (two groups, n=10 each) were treated with abamectin (0.2 mg/kg SC) alone or in combination with ivermectin (0.2 mg/kg SC) and itraconazole (30 mL PO). Drug/metabolite concentrations in plasma were measured (days 0-15). The faecal egg count reduction test (FECRT) was used as a measure of nematodicidal efficacy.ResultsExperiment 1: Coadministration resulted in an increase in both the plasma AUC0-LOQ and MRT of the metabolite fenbendazole sulfone (p<0.05), whereas all the PK parameters for triclabendazole sulfone were significantly decreased. Efficacy rose from 47.2 and 55.4 % (single administration) to 75.7 % (coadministration).Experiment 2: No differences in PK parameters were observed upon coadministration. Efficacies were 77.1 and 71.2 %, respectively, for the single and combined treatments. Experiment 3: Exposure to ivermectin and itraconazole resulted in an increase in abamectin Cmax and AUC0-LOQ (not significant). Efficacies were 0 % for both treatments.ConclusionsCombination of active principles with modulators and other active compounds has been advocated as an alternative to enhance anthelmintic efficacy. However, clinical efficacy against resistant nematodes remains elusive in practical terms. In spite of proven in vitro pharmacological interactions, translation to clinical settings shows that in vivo trials are needed in order to assess the real impact of modulators and combined therapies in parasite control.
Fil: Viviani, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Virkel, Guillermo Leon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Luque, Sonia Elisabet. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Lloberas, Maria Mercedes. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Agencia de Extensión Rural Balcarce; Argentina
Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
14th International Congress of the European Association for Veterinary Pharmacology and Toxicology
Wroclaw
Polonia
European Association for Veterinary Pharmacology and Toxicology
Materia
Metabolism
Transport
Anthelmintics
Ruminants
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:11336/174024
Acceder
id CONICETDig_406ed8ceb6e00ff4a3e5fc3cc7965f92
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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Modulation of metabolic and transport processes: a valuable tool for improving anthelmintic efficacy?Viviani, PaulaVirkel, Guillermo LeonLuque, Sonia ElisabetLloberas, Maria MercedesLanusse, Carlos EdmundoLifschitz, Adrian LuisMetabolismTransportAnthelminticsRuminantshttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4In vivo modulation of drug metabolizing enzymes and transporters may delay the elimination and enhance the systemic availability of anthelmintic compounds. Parasite exposure to the active molecules can be enhanced through their combination with transport modulators or other active anthelmintics. However, the practical relevance of such interactions is unknown. This work aims at assessing the occurrence of PK/PD interactions between (a) oxfendazole and triclabendazole; (b) moxidectin and loperamide; and (c) abamectin and ivermectin/itraconazole in lambs.Materials and MethodsLambs parasitized with nematodes highly resistant to benzimidazole and macrocyclic lactones were used.Experiment 1: Lambs (three groups, n=7 each) were treated with oxfendazole (5 mg/kg PO), triclabendazole (12 mg/kg PO) or their combination;Experiment 2: Lambs (two groups, n=7 each) were treated with moxidectin (0.2 mg/kg SC) alone or in combination with loperamide (0.16 mg/kg PO) and pluronic 123;Experiment 3: Lambs (two groups, n=10 each) were treated with abamectin (0.2 mg/kg SC) alone or in combination with ivermectin (0.2 mg/kg SC) and itraconazole (30 mL PO). Drug/metabolite concentrations in plasma were measured (days 0-15). The faecal egg count reduction test (FECRT) was used as a measure of nematodicidal efficacy.ResultsExperiment 1: Coadministration resulted in an increase in both the plasma AUC0-LOQ and MRT of the metabolite fenbendazole sulfone (p<0.05), whereas all the PK parameters for triclabendazole sulfone were significantly decreased. Efficacy rose from 47.2 and 55.4 % (single administration) to 75.7 % (coadministration).Experiment 2: No differences in PK parameters were observed upon coadministration. Efficacies were 77.1 and 71.2 %, respectively, for the single and combined treatments. Experiment 3: Exposure to ivermectin and itraconazole resulted in an increase in abamectin Cmax and AUC0-LOQ (not significant). Efficacies were 0 % for both treatments.ConclusionsCombination of active principles with modulators and other active compounds has been advocated as an alternative to enhance anthelmintic efficacy. However, clinical efficacy against resistant nematodes remains elusive in practical terms. In spite of proven in vitro pharmacological interactions, translation to clinical settings shows that in vivo trials are needed in order to assess the real impact of modulators and combined therapies in parasite control.Fil: Viviani, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Virkel, Guillermo Leon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Luque, Sonia Elisabet. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Lloberas, Maria Mercedes. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Agencia de Extensión Rural Balcarce; ArgentinaFil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina14th International Congress of the European Association for Veterinary Pharmacology and ToxicologyWroclawPoloniaEuropean Association for Veterinary Pharmacology and ToxicologyWiley2018info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/mswordapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/pdfhttp://hdl.handle.net/11336/174024Modulation of metabolic and transport processes: a valuable tool for improving anthelmintic efficacy?; 14th International Congress of the European Association for Veterinary Pharmacology and Toxicology; Wroclaw; Polonia; 2018; 73-740140-77831365-2885CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://web.archive.org/web/20180502161055/https://eavpt2018.pl/info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/toc/13652885/2018/41/S1Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-12T10:00:32Zoai:ri.conicet.gov.ar:11336/174024instacron: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:34982025-11-12 10:00:32.439CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Modulation of metabolic and transport processes: a valuable tool for improving anthelmintic efficacy?
title Modulation of metabolic and transport processes: a valuable tool for improving anthelmintic efficacy?
spellingShingle Modulation of metabolic and transport processes: a valuable tool for improving anthelmintic efficacy?
Viviani, Paula
Metabolism
Transport
Anthelmintics
Ruminants
title_short Modulation of metabolic and transport processes: a valuable tool for improving anthelmintic efficacy?
title_full Modulation of metabolic and transport processes: a valuable tool for improving anthelmintic efficacy?
title_fullStr Modulation of metabolic and transport processes: a valuable tool for improving anthelmintic efficacy?
title_full_unstemmed Modulation of metabolic and transport processes: a valuable tool for improving anthelmintic efficacy?
title_sort Modulation of metabolic and transport processes: a valuable tool for improving anthelmintic efficacy?
dc.creator.none.fl_str_mv Viviani, Paula
Virkel, Guillermo Leon
Luque, Sonia Elisabet
Lloberas, Maria Mercedes
Lanusse, Carlos Edmundo
Lifschitz, Adrian Luis
author Viviani, Paula
author_facet Viviani, Paula
Virkel, Guillermo Leon
Luque, Sonia Elisabet
Lloberas, Maria Mercedes
Lanusse, Carlos Edmundo
Lifschitz, Adrian Luis
author_role author
author2 Virkel, Guillermo Leon
Luque, Sonia Elisabet
Lloberas, Maria Mercedes
Lanusse, Carlos Edmundo
Lifschitz, Adrian Luis
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Metabolism
Transport
Anthelmintics
Ruminants
topic Metabolism
Transport
Anthelmintics
Ruminants
purl_subject.fl_str_mv https://purl.org/becyt/ford/4.3
https://purl.org/becyt/ford/4
dc.description.none.fl_txt_mv In vivo modulation of drug metabolizing enzymes and transporters may delay the elimination and enhance the systemic availability of anthelmintic compounds. Parasite exposure to the active molecules can be enhanced through their combination with transport modulators or other active anthelmintics. However, the practical relevance of such interactions is unknown. This work aims at assessing the occurrence of PK/PD interactions between (a) oxfendazole and triclabendazole; (b) moxidectin and loperamide; and (c) abamectin and ivermectin/itraconazole in lambs.Materials and MethodsLambs parasitized with nematodes highly resistant to benzimidazole and macrocyclic lactones were used.Experiment 1: Lambs (three groups, n=7 each) were treated with oxfendazole (5 mg/kg PO), triclabendazole (12 mg/kg PO) or their combination;Experiment 2: Lambs (two groups, n=7 each) were treated with moxidectin (0.2 mg/kg SC) alone or in combination with loperamide (0.16 mg/kg PO) and pluronic 123;Experiment 3: Lambs (two groups, n=10 each) were treated with abamectin (0.2 mg/kg SC) alone or in combination with ivermectin (0.2 mg/kg SC) and itraconazole (30 mL PO). Drug/metabolite concentrations in plasma were measured (days 0-15). The faecal egg count reduction test (FECRT) was used as a measure of nematodicidal efficacy.ResultsExperiment 1: Coadministration resulted in an increase in both the plasma AUC0-LOQ and MRT of the metabolite fenbendazole sulfone (p<0.05), whereas all the PK parameters for triclabendazole sulfone were significantly decreased. Efficacy rose from 47.2 and 55.4 % (single administration) to 75.7 % (coadministration).Experiment 2: No differences in PK parameters were observed upon coadministration. Efficacies were 77.1 and 71.2 %, respectively, for the single and combined treatments. Experiment 3: Exposure to ivermectin and itraconazole resulted in an increase in abamectin Cmax and AUC0-LOQ (not significant). Efficacies were 0 % for both treatments.ConclusionsCombination of active principles with modulators and other active compounds has been advocated as an alternative to enhance anthelmintic efficacy. However, clinical efficacy against resistant nematodes remains elusive in practical terms. In spite of proven in vitro pharmacological interactions, translation to clinical settings shows that in vivo trials are needed in order to assess the real impact of modulators and combined therapies in parasite control.
Fil: Viviani, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Virkel, Guillermo Leon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Luque, Sonia Elisabet. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Lloberas, Maria Mercedes. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Agencia de Extensión Rural Balcarce; Argentina
Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
14th International Congress of the European Association for Veterinary Pharmacology and Toxicology
Wroclaw
Polonia
European Association for Veterinary Pharmacology and Toxicology
description In vivo modulation of drug metabolizing enzymes and transporters may delay the elimination and enhance the systemic availability of anthelmintic compounds. Parasite exposure to the active molecules can be enhanced through their combination with transport modulators or other active anthelmintics. However, the practical relevance of such interactions is unknown. This work aims at assessing the occurrence of PK/PD interactions between (a) oxfendazole and triclabendazole; (b) moxidectin and loperamide; and (c) abamectin and ivermectin/itraconazole in lambs.Materials and MethodsLambs parasitized with nematodes highly resistant to benzimidazole and macrocyclic lactones were used.Experiment 1: Lambs (three groups, n=7 each) were treated with oxfendazole (5 mg/kg PO), triclabendazole (12 mg/kg PO) or their combination;Experiment 2: Lambs (two groups, n=7 each) were treated with moxidectin (0.2 mg/kg SC) alone or in combination with loperamide (0.16 mg/kg PO) and pluronic 123;Experiment 3: Lambs (two groups, n=10 each) were treated with abamectin (0.2 mg/kg SC) alone or in combination with ivermectin (0.2 mg/kg SC) and itraconazole (30 mL PO). Drug/metabolite concentrations in plasma were measured (days 0-15). The faecal egg count reduction test (FECRT) was used as a measure of nematodicidal efficacy.ResultsExperiment 1: Coadministration resulted in an increase in both the plasma AUC0-LOQ and MRT of the metabolite fenbendazole sulfone (p<0.05), whereas all the PK parameters for triclabendazole sulfone were significantly decreased. Efficacy rose from 47.2 and 55.4 % (single administration) to 75.7 % (coadministration).Experiment 2: No differences in PK parameters were observed upon coadministration. Efficacies were 77.1 and 71.2 %, respectively, for the single and combined treatments. Experiment 3: Exposure to ivermectin and itraconazole resulted in an increase in abamectin Cmax and AUC0-LOQ (not significant). Efficacies were 0 % for both treatments.ConclusionsCombination of active principles with modulators and other active compounds has been advocated as an alternative to enhance anthelmintic efficacy. However, clinical efficacy against resistant nematodes remains elusive in practical terms. In spite of proven in vitro pharmacological interactions, translation to clinical settings shows that in vivo trials are needed in order to assess the real impact of modulators and combined therapies in parasite control.
publishDate 2018
dc.date.none.fl_str_mv 2018
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info:eu-repo/semantics/conferenceObject
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http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/174024
Modulation of metabolic and transport processes: a valuable tool for improving anthelmintic efficacy?; 14th International Congress of the European Association for Veterinary Pharmacology and Toxicology; Wroclaw; Polonia; 2018; 73-74
0140-7783
1365-2885
CONICET Digital
CONICET
url http://hdl.handle.net/11336/174024
identifier_str_mv Modulation of metabolic and transport processes: a valuable tool for improving anthelmintic efficacy?; 14th International Congress of the European Association for Veterinary Pharmacology and Toxicology; Wroclaw; Polonia; 2018; 73-74
0140-7783
1365-2885
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
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