Phytochemicals in Gastrointestinal Nematode Control: Pharmacokinetic–Pharmacodynamic Evaluation of the Ivermectin plus Carvone Combination

Autores
Miró, María Victoria; Costa Júnior, Livio M.; Lloberas, María Mercedes; Cardozo, Patricia Alejandra; Lanusse, Carlos; Virkel, Guillermo; Lifschitz, Adrián
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A wide variety of plant-derived phytochemicals with anthelmintic effects have been described. Most of them have shown activity against parasites in vitro but have not been extensively explored in vivo. The aim of the current work was to study the pharmacokinetic–pharmacodynamic relationship of the combined administration of carvone (R-CNE) and ivermectin (IVM) to lambs. Three trials were conducted to evaluate the pharmacological interaction between R-CNE and IVM in lambs infected with resistant nematodes. Drug concentrations were measured in plasma, target tissues, and H. contortus by HPLC with fluorescent (IVM) and ultraviolet (R-CNE) detection. The effect of both compounds on parasites was estimated by the fecal egg count reduction. Coadministration with R-CNE significantly increased the plasma bioavailability of IVM. R-CNE showed a moderate anthelmintic effect, which was greater on the susceptible isolate of H. contortus. After the combination of R-CNE and IVM as an oral emulsion, both compounds were quantified in H. contortus recovered from infected lambs. However, R-CNE concentrations were much lower than those reported to achieve anthelmintic effects in the in vitro assays. Optimization of the pharmaceutical formulation, dose rate, and administration schedule is needed to take advantage of the intrinsic anthelmintic activity of phytochemicals.
EEA Balcarce
Fil: Miró, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires; Argentina. Centro de Investigación Veterinaria de Tandil; Argentina.
Fil: Costa Júnior, Livio M. Federal University of Maranhão. Center for Biological and Health Sciences; Brasil.
Fil: Lloberas, Mercedes. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina.
Fil: Cardozo, Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA), Estación Experimental Agropecuaria Balcarce; Argentina.
Fil: Lanusse, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires; Argentina. Centro de Investigación Veterinaria de Tandil; Argentina.
Fil: Virkel, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires; Argentina. Centro de Investigación Veterinaria de Tandil; Argentina.
Fil: Lifschitz, Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires; Argentina. Centro de Investigación Veterinaria de Tandil; Argentina.
Fuente
Animals 13 (8) : 1287 (April 2023)
Materia
Nematodos
Cordero
Farmacocinética
Farmacodinámica
Nematodes
Lambs
Pharmacokinetics
Pharmacodynamics
Fitoquímicos
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/15149
Acceder
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oai_identifier_str oai:localhost:20.500.12123/15149
network_acronym_str INTADig
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network_name_str INTA Digital (INTA)
spelling Phytochemicals in Gastrointestinal Nematode Control: Pharmacokinetic–Pharmacodynamic Evaluation of the Ivermectin plus Carvone CombinationMiró, María VictoriaCosta Júnior, Livio M.Lloberas, María MercedesCardozo, Patricia AlejandraLanusse, CarlosVirkel, GuillermoLifschitz, AdriánNematodosCorderoFarmacocinéticaFarmacodinámicaNematodesLambsPharmacokineticsPharmacodynamicsFitoquímicosA wide variety of plant-derived phytochemicals with anthelmintic effects have been described. Most of them have shown activity against parasites in vitro but have not been extensively explored in vivo. The aim of the current work was to study the pharmacokinetic–pharmacodynamic relationship of the combined administration of carvone (R-CNE) and ivermectin (IVM) to lambs. Three trials were conducted to evaluate the pharmacological interaction between R-CNE and IVM in lambs infected with resistant nematodes. Drug concentrations were measured in plasma, target tissues, and H. contortus by HPLC with fluorescent (IVM) and ultraviolet (R-CNE) detection. The effect of both compounds on parasites was estimated by the fecal egg count reduction. Coadministration with R-CNE significantly increased the plasma bioavailability of IVM. R-CNE showed a moderate anthelmintic effect, which was greater on the susceptible isolate of H. contortus. After the combination of R-CNE and IVM as an oral emulsion, both compounds were quantified in H. contortus recovered from infected lambs. However, R-CNE concentrations were much lower than those reported to achieve anthelmintic effects in the in vitro assays. Optimization of the pharmaceutical formulation, dose rate, and administration schedule is needed to take advantage of the intrinsic anthelmintic activity of phytochemicals.EEA BalcarceFil: Miró, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires; Argentina. Centro de Investigación Veterinaria de Tandil; Argentina.Fil: Costa Júnior, Livio M. Federal University of Maranhão. Center for Biological and Health Sciences; Brasil.Fil: Lloberas, Mercedes. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina.Fil: Cardozo, Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA), Estación Experimental Agropecuaria Balcarce; Argentina.Fil: Lanusse, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires; Argentina. Centro de Investigación Veterinaria de Tandil; Argentina.Fil: Virkel, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires; Argentina. Centro de Investigación Veterinaria de Tandil; Argentina.Fil: Lifschitz, Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires; Argentina. Centro de Investigación Veterinaria de Tandil; Argentina.Multidisciplinary Digital Publishing Institute, MDPI2023-09-08T13:12:18Z2023-09-08T13:12:18Z2023-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/15149https://www.mdpi.com/2076-2615/13/8/12872076-2615https://doi.org/10.3390/ani13081287Animals 13 (8) : 1287 (April 2023)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2025-09-04T09:49:55Zoai:localhost:20.500.12123/15149instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-09-04 09:49:55.82INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Phytochemicals in Gastrointestinal Nematode Control: Pharmacokinetic–Pharmacodynamic Evaluation of the Ivermectin plus Carvone Combination
title Phytochemicals in Gastrointestinal Nematode Control: Pharmacokinetic–Pharmacodynamic Evaluation of the Ivermectin plus Carvone Combination
spellingShingle Phytochemicals in Gastrointestinal Nematode Control: Pharmacokinetic–Pharmacodynamic Evaluation of the Ivermectin plus Carvone Combination
Miró, María Victoria
Nematodos
Cordero
Farmacocinética
Farmacodinámica
Nematodes
Lambs
Pharmacokinetics
Pharmacodynamics
Fitoquímicos
title_short Phytochemicals in Gastrointestinal Nematode Control: Pharmacokinetic–Pharmacodynamic Evaluation of the Ivermectin plus Carvone Combination
title_full Phytochemicals in Gastrointestinal Nematode Control: Pharmacokinetic–Pharmacodynamic Evaluation of the Ivermectin plus Carvone Combination
title_fullStr Phytochemicals in Gastrointestinal Nematode Control: Pharmacokinetic–Pharmacodynamic Evaluation of the Ivermectin plus Carvone Combination
title_full_unstemmed Phytochemicals in Gastrointestinal Nematode Control: Pharmacokinetic–Pharmacodynamic Evaluation of the Ivermectin plus Carvone Combination
title_sort Phytochemicals in Gastrointestinal Nematode Control: Pharmacokinetic–Pharmacodynamic Evaluation of the Ivermectin plus Carvone Combination
dc.creator.none.fl_str_mv Miró, María Victoria
Costa Júnior, Livio M.
Lloberas, María Mercedes
Cardozo, Patricia Alejandra
Lanusse, Carlos
Virkel, Guillermo
Lifschitz, Adrián
author Miró, María Victoria
author_facet Miró, María Victoria
Costa Júnior, Livio M.
Lloberas, María Mercedes
Cardozo, Patricia Alejandra
Lanusse, Carlos
Virkel, Guillermo
Lifschitz, Adrián
author_role author
author2 Costa Júnior, Livio M.
Lloberas, María Mercedes
Cardozo, Patricia Alejandra
Lanusse, Carlos
Virkel, Guillermo
Lifschitz, Adrián
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Nematodos
Cordero
Farmacocinética
Farmacodinámica
Nematodes
Lambs
Pharmacokinetics
Pharmacodynamics
Fitoquímicos
topic Nematodos
Cordero
Farmacocinética
Farmacodinámica
Nematodes
Lambs
Pharmacokinetics
Pharmacodynamics
Fitoquímicos
dc.description.none.fl_txt_mv A wide variety of plant-derived phytochemicals with anthelmintic effects have been described. Most of them have shown activity against parasites in vitro but have not been extensively explored in vivo. The aim of the current work was to study the pharmacokinetic–pharmacodynamic relationship of the combined administration of carvone (R-CNE) and ivermectin (IVM) to lambs. Three trials were conducted to evaluate the pharmacological interaction between R-CNE and IVM in lambs infected with resistant nematodes. Drug concentrations were measured in plasma, target tissues, and H. contortus by HPLC with fluorescent (IVM) and ultraviolet (R-CNE) detection. The effect of both compounds on parasites was estimated by the fecal egg count reduction. Coadministration with R-CNE significantly increased the plasma bioavailability of IVM. R-CNE showed a moderate anthelmintic effect, which was greater on the susceptible isolate of H. contortus. After the combination of R-CNE and IVM as an oral emulsion, both compounds were quantified in H. contortus recovered from infected lambs. However, R-CNE concentrations were much lower than those reported to achieve anthelmintic effects in the in vitro assays. Optimization of the pharmaceutical formulation, dose rate, and administration schedule is needed to take advantage of the intrinsic anthelmintic activity of phytochemicals.
EEA Balcarce
Fil: Miró, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires; Argentina. Centro de Investigación Veterinaria de Tandil; Argentina.
Fil: Costa Júnior, Livio M. Federal University of Maranhão. Center for Biological and Health Sciences; Brasil.
Fil: Lloberas, Mercedes. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina.
Fil: Cardozo, Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA), Estación Experimental Agropecuaria Balcarce; Argentina.
Fil: Lanusse, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires; Argentina. Centro de Investigación Veterinaria de Tandil; Argentina.
Fil: Virkel, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires; Argentina. Centro de Investigación Veterinaria de Tandil; Argentina.
Fil: Lifschitz, Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires; Argentina. Centro de Investigación Veterinaria de Tandil; Argentina.
description A wide variety of plant-derived phytochemicals with anthelmintic effects have been described. Most of them have shown activity against parasites in vitro but have not been extensively explored in vivo. The aim of the current work was to study the pharmacokinetic–pharmacodynamic relationship of the combined administration of carvone (R-CNE) and ivermectin (IVM) to lambs. Three trials were conducted to evaluate the pharmacological interaction between R-CNE and IVM in lambs infected with resistant nematodes. Drug concentrations were measured in plasma, target tissues, and H. contortus by HPLC with fluorescent (IVM) and ultraviolet (R-CNE) detection. The effect of both compounds on parasites was estimated by the fecal egg count reduction. Coadministration with R-CNE significantly increased the plasma bioavailability of IVM. R-CNE showed a moderate anthelmintic effect, which was greater on the susceptible isolate of H. contortus. After the combination of R-CNE and IVM as an oral emulsion, both compounds were quantified in H. contortus recovered from infected lambs. However, R-CNE concentrations were much lower than those reported to achieve anthelmintic effects in the in vitro assays. Optimization of the pharmaceutical formulation, dose rate, and administration schedule is needed to take advantage of the intrinsic anthelmintic activity of phytochemicals.
publishDate 2023
dc.date.none.fl_str_mv 2023-09-08T13:12:18Z
2023-09-08T13:12:18Z
2023-04
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/20.500.12123/15149
https://www.mdpi.com/2076-2615/13/8/1287
2076-2615
https://doi.org/10.3390/ani13081287
url http://hdl.handle.net/20.500.12123/15149
https://www.mdpi.com/2076-2615/13/8/1287
https://doi.org/10.3390/ani13081287
identifier_str_mv 2076-2615
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute, MDPI
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute, MDPI
dc.source.none.fl_str_mv Animals 13 (8) : 1287 (April 2023)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
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