Phytochemical-Mediated Modulation of Doramectin Pharmacology in Sheep: Exploring the Cinnamaldehyde–Pink Grapefruit Combination

Autores
Miró, María Victoria; Ichinose, Paula; Lloberas, María Mercedes; Moriones, Lucila; Lanusse, Carlos; Virkel, Guillermo; Lifschitz, Adrián
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Phytotherapy represents a promising field for developing new therapeutic strategies, either by acting as antiparasitic agents themselves or by enhancing the efficacy of synthetic drugs. The present study evaluated the in vivo pharmacokinetic and pharmacodynamic interactions following the administration of doramectin, either alone or in combination with cinnamaldehyde and pink grapefruit essential oil (CNM–PGF). Additionally, ex vivo P-glycoprotein-mediated interactions were assessed at the intestinal level. Higher efficacy against Haemonchus contortus was observed with the combined treatment of doramectin plus phytochemicals or loperamide. Although phytochemicals and loperamide reduced the ex vivo efflux of rhodamine 123, no pharmacokinetic interactions were detected in vivo. The enhanced efficacy is most likely attributable to localized drug–drug interactions and increased drug availability at the parasite interface. Based on the results obtained, the best treatment would be the combination of DRM with phytochemicals such as CNM–PGF and loperamide. However, a pharmaceutical formulation that allows sustained in vivo interaction between these compounds is needed.
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: Ichinose, Paula. 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: Lloberas, Mercedes. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina
Fil: Moriones, Lucila. 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: 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 15 (17) : 2539 (August 2025)
Materia
Oveja
Nematodos
Medicamento Veterinario
Farmacología
Compuestos Orgánicos
Resistencia a los Antihelmínticos
Glicoproteínas
Ewes
Nematodes
Trypanocidal Drugs
Pharmacology
Organic Compounds
Resistance to Anthelmintics
Glycoproteins
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:20.500.12123/24402
Acceder
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oai_identifier_str oai:localhost:20.500.12123/24402
network_acronym_str INTADig
repository_id_str l
network_name_str INTA Digital (INTA)
spelling Phytochemical-Mediated Modulation of Doramectin Pharmacology in Sheep: Exploring the Cinnamaldehyde–Pink Grapefruit CombinationMiró, María VictoriaIchinose, PaulaLloberas, María MercedesMoriones, LucilaLanusse, CarlosVirkel, GuillermoLifschitz, AdriánOvejaNematodosMedicamento VeterinarioFarmacologíaCompuestos OrgánicosResistencia a los AntihelmínticosGlicoproteínasEwesNematodesTrypanocidal DrugsPharmacologyOrganic CompoundsResistance to AnthelminticsGlycoproteinsPhytotherapy represents a promising field for developing new therapeutic strategies, either by acting as antiparasitic agents themselves or by enhancing the efficacy of synthetic drugs. The present study evaluated the in vivo pharmacokinetic and pharmacodynamic interactions following the administration of doramectin, either alone or in combination with cinnamaldehyde and pink grapefruit essential oil (CNM–PGF). Additionally, ex vivo P-glycoprotein-mediated interactions were assessed at the intestinal level. Higher efficacy against Haemonchus contortus was observed with the combined treatment of doramectin plus phytochemicals or loperamide. Although phytochemicals and loperamide reduced the ex vivo efflux of rhodamine 123, no pharmacokinetic interactions were detected in vivo. The enhanced efficacy is most likely attributable to localized drug–drug interactions and increased drug availability at the parasite interface. Based on the results obtained, the best treatment would be the combination of DRM with phytochemicals such as CNM–PGF and loperamide. However, a pharmaceutical formulation that allows sustained in vivo interaction between these compounds is needed.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; ArgentinaFil: Ichinose, Paula. 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; ArgentinaFil: Lloberas, Mercedes. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Moriones, Lucila. 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; ArgentinaFil: 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; ArgentinaFil. 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; ArgentinaFil: 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; ArgentinaMultidisciplinary Digital Publishing Institute, MDPI2025-10-31T10:53:20Z2025-10-31T10:53:20Z2025-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/24402https://www.mdpi.com/2076-2615/15/17/25392076-2615https://doi.org/10.3390/ani15172539Animals 15 (17) : 2539 (August 2025)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)2025-11-13T08:48:47Zoai:localhost:20.500.12123/24402instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-11-13 08:48:47.971INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Phytochemical-Mediated Modulation of Doramectin Pharmacology in Sheep: Exploring the Cinnamaldehyde–Pink Grapefruit Combination
title Phytochemical-Mediated Modulation of Doramectin Pharmacology in Sheep: Exploring the Cinnamaldehyde–Pink Grapefruit Combination
spellingShingle Phytochemical-Mediated Modulation of Doramectin Pharmacology in Sheep: Exploring the Cinnamaldehyde–Pink Grapefruit Combination
Miró, María Victoria
Oveja
Nematodos
Medicamento Veterinario
Farmacología
Compuestos Orgánicos
Resistencia a los Antihelmínticos
Glicoproteínas
Ewes
Nematodes
Trypanocidal Drugs
Pharmacology
Organic Compounds
Resistance to Anthelmintics
Glycoproteins
title_short Phytochemical-Mediated Modulation of Doramectin Pharmacology in Sheep: Exploring the Cinnamaldehyde–Pink Grapefruit Combination
title_full Phytochemical-Mediated Modulation of Doramectin Pharmacology in Sheep: Exploring the Cinnamaldehyde–Pink Grapefruit Combination
title_fullStr Phytochemical-Mediated Modulation of Doramectin Pharmacology in Sheep: Exploring the Cinnamaldehyde–Pink Grapefruit Combination
title_full_unstemmed Phytochemical-Mediated Modulation of Doramectin Pharmacology in Sheep: Exploring the Cinnamaldehyde–Pink Grapefruit Combination
title_sort Phytochemical-Mediated Modulation of Doramectin Pharmacology in Sheep: Exploring the Cinnamaldehyde–Pink Grapefruit Combination
dc.creator.none.fl_str_mv Miró, María Victoria
Ichinose, Paula
Lloberas, María Mercedes
Moriones, Lucila
Lanusse, Carlos
Virkel, Guillermo
Lifschitz, Adrián
author Miró, María Victoria
author_facet Miró, María Victoria
Ichinose, Paula
Lloberas, María Mercedes
Moriones, Lucila
Lanusse, Carlos
Virkel, Guillermo
Lifschitz, Adrián
author_role author
author2 Ichinose, Paula
Lloberas, María Mercedes
Moriones, Lucila
Lanusse, Carlos
Virkel, Guillermo
Lifschitz, Adrián
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Oveja
Nematodos
Medicamento Veterinario
Farmacología
Compuestos Orgánicos
Resistencia a los Antihelmínticos
Glicoproteínas
Ewes
Nematodes
Trypanocidal Drugs
Pharmacology
Organic Compounds
Resistance to Anthelmintics
Glycoproteins
topic Oveja
Nematodos
Medicamento Veterinario
Farmacología
Compuestos Orgánicos
Resistencia a los Antihelmínticos
Glicoproteínas
Ewes
Nematodes
Trypanocidal Drugs
Pharmacology
Organic Compounds
Resistance to Anthelmintics
Glycoproteins
dc.description.none.fl_txt_mv Phytotherapy represents a promising field for developing new therapeutic strategies, either by acting as antiparasitic agents themselves or by enhancing the efficacy of synthetic drugs. The present study evaluated the in vivo pharmacokinetic and pharmacodynamic interactions following the administration of doramectin, either alone or in combination with cinnamaldehyde and pink grapefruit essential oil (CNM–PGF). Additionally, ex vivo P-glycoprotein-mediated interactions were assessed at the intestinal level. Higher efficacy against Haemonchus contortus was observed with the combined treatment of doramectin plus phytochemicals or loperamide. Although phytochemicals and loperamide reduced the ex vivo efflux of rhodamine 123, no pharmacokinetic interactions were detected in vivo. The enhanced efficacy is most likely attributable to localized drug–drug interactions and increased drug availability at the parasite interface. Based on the results obtained, the best treatment would be the combination of DRM with phytochemicals such as CNM–PGF and loperamide. However, a pharmaceutical formulation that allows sustained in vivo interaction between these compounds is needed.
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: Ichinose, Paula. 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: Lloberas, Mercedes. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina
Fil: Moriones, Lucila. 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: 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 Phytotherapy represents a promising field for developing new therapeutic strategies, either by acting as antiparasitic agents themselves or by enhancing the efficacy of synthetic drugs. The present study evaluated the in vivo pharmacokinetic and pharmacodynamic interactions following the administration of doramectin, either alone or in combination with cinnamaldehyde and pink grapefruit essential oil (CNM–PGF). Additionally, ex vivo P-glycoprotein-mediated interactions were assessed at the intestinal level. Higher efficacy against Haemonchus contortus was observed with the combined treatment of doramectin plus phytochemicals or loperamide. Although phytochemicals and loperamide reduced the ex vivo efflux of rhodamine 123, no pharmacokinetic interactions were detected in vivo. The enhanced efficacy is most likely attributable to localized drug–drug interactions and increased drug availability at the parasite interface. Based on the results obtained, the best treatment would be the combination of DRM with phytochemicals such as CNM–PGF and loperamide. However, a pharmaceutical formulation that allows sustained in vivo interaction between these compounds is needed.
publishDate 2025
dc.date.none.fl_str_mv 2025-10-31T10:53:20Z
2025-10-31T10:53:20Z
2025-08
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/20.500.12123/24402
https://www.mdpi.com/2076-2615/15/17/2539
2076-2615
https://doi.org/10.3390/ani15172539
url http://hdl.handle.net/20.500.12123/24402
https://www.mdpi.com/2076-2615/15/17/2539
https://doi.org/10.3390/ani15172539
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 15 (17) : 2539 (August 2025)
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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score 12.738264

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