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

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 c...

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Autores principales: Miró, María Victoria, Costa Júnior, Livio M., Lloberas, María Mercedes, Cardozo, Patricia Alejandra, Lanusse, Carlos, Virkel, Guillermo, Lifschitz, Adrián
Formato: info:ar-repo/semantics/artículo
Lenguaje:Inglés
Publicado: Multidisciplinary Digital Publishing Institute, MDPI 2023
Materias:
Acceso en línea:http://hdl.handle.net/20.500.12123/15149
https://www.mdpi.com/2076-2615/13/8/1287
https://doi.org/10.3390/ani13081287
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author Miró, María Victoria
Costa Júnior, Livio M.
Lloberas, María Mercedes
Cardozo, Patricia Alejandra
Lanusse, Carlos
Virkel, Guillermo
Lifschitz, Adrián
author_browse Cardozo, Patricia Alejandra
Costa Júnior, Livio M.
Lanusse, Carlos
Lifschitz, Adrián
Lloberas, María Mercedes
Miró, María Victoria
Virkel, Guillermo
author_facet Miró, María Victoria
Costa Júnior, Livio M.
Lloberas, María Mercedes
Cardozo, Patricia Alejandra
Lanusse, Carlos
Virkel, Guillermo
Lifschitz, Adrián
author_sort Miró, María Victoria
collection INTA Digital
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.
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institution Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina)
language Inglés
publishDate 2023
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spelling INTA151492023-09-08T13:16:25Z Phytochemicals in Gastrointestinal Nematode Control: Pharmacokinetic–Pharmacodynamic Evaluation of the Ivermectin plus Carvone Combination Miró, María Victoria Costa Júnior, Livio M. Lloberas, María Mercedes Cardozo, Patricia Alejandra Lanusse, Carlos Virkel, Guillermo Lifschitz, Adrián Nematodos Cordero Farmacocinética Farmacodinámica Nematodes Lambs Pharmacokinetics Pharmacodynamics Fitoquímicos 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. 2023-09-08T13:12:18Z 2023-09-08T13:12:18Z 2023-04 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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 eng 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) application/pdf Multidisciplinary Digital Publishing Institute, MDPI Animals 13 (8) : 1287 (April 2023)
spellingShingle Nematodos
Cordero
Farmacocinética
Farmacodinámica
Nematodes
Lambs
Pharmacokinetics
Pharmacodynamics
Fitoquímicos
Miró, María Victoria
Costa Júnior, Livio M.
Lloberas, María Mercedes
Cardozo, Patricia Alejandra
Lanusse, Carlos
Virkel, Guillermo
Lifschitz, Adrián
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
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_short 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
topic Nematodos
Cordero
Farmacocinética
Farmacodinámica
Nematodes
Lambs
Pharmacokinetics
Pharmacodynamics
Fitoquímicos
url http://hdl.handle.net/20.500.12123/15149
https://www.mdpi.com/2076-2615/13/8/1287
https://doi.org/10.3390/ani13081287
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