Evaluation of dose escalation and drug combinations of ivermectin and fipronil as strategies for improving control of resistant Rhipicephalus microplus populations

Autores
Sarli, Macarena; Rossner, Maria Victoria; Torrents, Jorgelina; Miró, María Victoria; Lifschitz, Adrián Luis; Nava, Santiago
Año de publicación
2026
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The objective of this study was to compare the therapeutic and pharmacological performance of ivermectin (IVM) and fipronil (FIP) administered as single drugs, combined in a same formulation, or co-administered individually, as potential strategies to improve treatment efficacy against multi-resistant Rhipicephalus microplus populations. The effect of IVM dose escalation was also evaluated. Naturally infested heifers were allocated into six groups (G) and treated with: injectable IVM 1% at 0.2 mg/kg (G-I) or 0.4 mg/kg (G-II); FIP pour-on at 1 mg/kg (G-III); pour-on formulation of IVM/FIP (0.5 mg/kg IVM + 1 mg/kg FIP; G-IV); co-administration of injectable IVM (0.2 mg/kg) and pour-on FIP (1 mg/kg; G-V); untreated (G-VI). IVM and FIP concentrations in plasma and ticks were quantified by HPLC. Absolute control was not achieved in any treated group. Therapeutic efficacy ranged from 66 to 82.6%, 88.0–97.3%, and 75.7–96.9% at days 3, 7, and 9 post-treatment, respectively, and outlier animals with high tick counts were consistently observed. Although significantly higher plasma IVM concentrations were achieved with the double dose, efficacy was not improved compared with the standard dose. Cattle treated with the pour-on combination showed markedly lower plasma IVM levels due to reduced topical absorption. Co-administration of individual drugs produced pharmacokinetic profiles similar to single-drug treatments. Neither IVM dose escalation nor IVM-FIP combinations improve therapeutic outcomes compared with those obtained with mono-drug formulations. When simultaneous use is required, co-administration of IVM and FIP is preferable to combined pour-on formulations because IVM absorption is better as injectable than in topical administration.
EEA Rafaela
Fil: Sarli, Macarena. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela. Instituto de Investigación de la Cadena Láctea (IDICAL); Argentina
Fil: Sarli, Macarena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación de la Cadena Láctea (IDICAL); Argentina
Fil: Rossner, Maria Victoria. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Colonia Benitez; Argentina
Fil: Torrents, Jorgelina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela. Instituto de Investigación de la Cadena Láctea (IDICAL); Argentina
Fil: Torrents, Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación de la Cadena Láctea (IDICAL); Argentina
Fil: Miró, V. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Centro de Investigación Veterinaria de Tandil (CIVETAN). Laboratorio de Farmacología; Argentina.
Fil: Miró, V. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación Veterinaria de Tandil (CIVETAN); Argentina
Fil: Lifschitz, Adrian. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Centro de Investigación Veterinaria de Tandil (CIVETAN). Laboratorio de Farmacología; Argentina.
Fil: Lifschitz, Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación Veterinaria de Tandil (CIVETAN); Argentina
Fil: Nava, Santiago. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela. Instituto de Investigación de la Cadena Láctea (IDICAL); Argentina
Fil: Nava, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación de la Cadena Láctea (IDICAL); Argentina
Fuente
Veterinary Research Communications 50 : article number 172. (2026)
Materia
Garrapatas
Control de Plagas
Ivermectina
Acaricidas
Dosis de Aplicación
Ticks
Rhipicephalus
Pest Control
Ivermectin
Fipronil
Acaricides
Application Rates
Rhipicephalus microplus
Nivel de accesibilidad
acceso restringido
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:20.500.12123/27070

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network_name_str INTA Digital (INTA)
spelling Evaluation of dose escalation and drug combinations of ivermectin and fipronil as strategies for improving control of resistant Rhipicephalus microplus populationsSarli, MacarenaRossner, Maria VictoriaTorrents, JorgelinaMiró, María VictoriaLifschitz, Adrián LuisNava, SantiagoGarrapatasControl de PlagasIvermectinaAcaricidasDosis de AplicaciónTicksRhipicephalusPest ControlIvermectinFipronilAcaricidesApplication RatesRhipicephalus microplusThe objective of this study was to compare the therapeutic and pharmacological performance of ivermectin (IVM) and fipronil (FIP) administered as single drugs, combined in a same formulation, or co-administered individually, as potential strategies to improve treatment efficacy against multi-resistant Rhipicephalus microplus populations. The effect of IVM dose escalation was also evaluated. Naturally infested heifers were allocated into six groups (G) and treated with: injectable IVM 1% at 0.2 mg/kg (G-I) or 0.4 mg/kg (G-II); FIP pour-on at 1 mg/kg (G-III); pour-on formulation of IVM/FIP (0.5 mg/kg IVM + 1 mg/kg FIP; G-IV); co-administration of injectable IVM (0.2 mg/kg) and pour-on FIP (1 mg/kg; G-V); untreated (G-VI). IVM and FIP concentrations in plasma and ticks were quantified by HPLC. Absolute control was not achieved in any treated group. Therapeutic efficacy ranged from 66 to 82.6%, 88.0–97.3%, and 75.7–96.9% at days 3, 7, and 9 post-treatment, respectively, and outlier animals with high tick counts were consistently observed. Although significantly higher plasma IVM concentrations were achieved with the double dose, efficacy was not improved compared with the standard dose. Cattle treated with the pour-on combination showed markedly lower plasma IVM levels due to reduced topical absorption. Co-administration of individual drugs produced pharmacokinetic profiles similar to single-drug treatments. Neither IVM dose escalation nor IVM-FIP combinations improve therapeutic outcomes compared with those obtained with mono-drug formulations. When simultaneous use is required, co-administration of IVM and FIP is preferable to combined pour-on formulations because IVM absorption is better as injectable than in topical administration.EEA RafaelaFil: Sarli, Macarena. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela. Instituto de Investigación de la Cadena Láctea (IDICAL); ArgentinaFil: Sarli, Macarena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación de la Cadena Láctea (IDICAL); ArgentinaFil: Rossner, Maria Victoria. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Colonia Benitez; ArgentinaFil: Torrents, Jorgelina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela. Instituto de Investigación de la Cadena Láctea (IDICAL); ArgentinaFil: Torrents, Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación de la Cadena Láctea (IDICAL); ArgentinaFil: Miró, V. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Centro de Investigación Veterinaria de Tandil (CIVETAN). Laboratorio de Farmacología; Argentina.Fil: Miró, V. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación Veterinaria de Tandil (CIVETAN); ArgentinaFil: Lifschitz, Adrian. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Centro de Investigación Veterinaria de Tandil (CIVETAN). Laboratorio de Farmacología; Argentina.Fil: Lifschitz, Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación Veterinaria de Tandil (CIVETAN); ArgentinaFil: Nava, Santiago. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela. Instituto de Investigación de la Cadena Láctea (IDICAL); ArgentinaFil: Nava, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación de la Cadena Láctea (IDICAL); ArgentinaSpringer2026-07-20T12:10:38Z2026-07-20T12:10:38Z2026-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/27070https://link.springer.com/article/10.1007/s11259-026-11125-30165-73801573-7446https://doi.org/10.1007/s11259-026-11125-3Veterinary Research Communications 50 : article number 172. (2026)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/restrictedAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2026-09-24T11:43:29Zoai:localhost:20.500.12123/27070instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2026-09-24 11:43:30.37INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Evaluation of dose escalation and drug combinations of ivermectin and fipronil as strategies for improving control of resistant Rhipicephalus microplus populations
title Evaluation of dose escalation and drug combinations of ivermectin and fipronil as strategies for improving control of resistant Rhipicephalus microplus populations
spellingShingle Evaluation of dose escalation and drug combinations of ivermectin and fipronil as strategies for improving control of resistant Rhipicephalus microplus populations
Sarli, Macarena
Garrapatas
Control de Plagas
Ivermectina
Acaricidas
Dosis de Aplicación
Ticks
Rhipicephalus
Pest Control
Ivermectin
Fipronil
Acaricides
Application Rates
Rhipicephalus microplus
title_short Evaluation of dose escalation and drug combinations of ivermectin and fipronil as strategies for improving control of resistant Rhipicephalus microplus populations
title_full Evaluation of dose escalation and drug combinations of ivermectin and fipronil as strategies for improving control of resistant Rhipicephalus microplus populations
title_fullStr Evaluation of dose escalation and drug combinations of ivermectin and fipronil as strategies for improving control of resistant Rhipicephalus microplus populations
title_full_unstemmed Evaluation of dose escalation and drug combinations of ivermectin and fipronil as strategies for improving control of resistant Rhipicephalus microplus populations
title_sort Evaluation of dose escalation and drug combinations of ivermectin and fipronil as strategies for improving control of resistant Rhipicephalus microplus populations
dc.creator.none.fl_str_mv Sarli, Macarena
Rossner, Maria Victoria
Torrents, Jorgelina
Miró, María Victoria
Lifschitz, Adrián Luis
Nava, Santiago
author Sarli, Macarena
author_facet Sarli, Macarena
Rossner, Maria Victoria
Torrents, Jorgelina
Miró, María Victoria
Lifschitz, Adrián Luis
Nava, Santiago
author_role author
author2 Rossner, Maria Victoria
Torrents, Jorgelina
Miró, María Victoria
Lifschitz, Adrián Luis
Nava, Santiago
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Garrapatas
Control de Plagas
Ivermectina
Acaricidas
Dosis de Aplicación
Ticks
Rhipicephalus
Pest Control
Ivermectin
Fipronil
Acaricides
Application Rates
Rhipicephalus microplus
topic Garrapatas
Control de Plagas
Ivermectina
Acaricidas
Dosis de Aplicación
Ticks
Rhipicephalus
Pest Control
Ivermectin
Fipronil
Acaricides
Application Rates
Rhipicephalus microplus
dc.description.none.fl_txt_mv The objective of this study was to compare the therapeutic and pharmacological performance of ivermectin (IVM) and fipronil (FIP) administered as single drugs, combined in a same formulation, or co-administered individually, as potential strategies to improve treatment efficacy against multi-resistant Rhipicephalus microplus populations. The effect of IVM dose escalation was also evaluated. Naturally infested heifers were allocated into six groups (G) and treated with: injectable IVM 1% at 0.2 mg/kg (G-I) or 0.4 mg/kg (G-II); FIP pour-on at 1 mg/kg (G-III); pour-on formulation of IVM/FIP (0.5 mg/kg IVM + 1 mg/kg FIP; G-IV); co-administration of injectable IVM (0.2 mg/kg) and pour-on FIP (1 mg/kg; G-V); untreated (G-VI). IVM and FIP concentrations in plasma and ticks were quantified by HPLC. Absolute control was not achieved in any treated group. Therapeutic efficacy ranged from 66 to 82.6%, 88.0–97.3%, and 75.7–96.9% at days 3, 7, and 9 post-treatment, respectively, and outlier animals with high tick counts were consistently observed. Although significantly higher plasma IVM concentrations were achieved with the double dose, efficacy was not improved compared with the standard dose. Cattle treated with the pour-on combination showed markedly lower plasma IVM levels due to reduced topical absorption. Co-administration of individual drugs produced pharmacokinetic profiles similar to single-drug treatments. Neither IVM dose escalation nor IVM-FIP combinations improve therapeutic outcomes compared with those obtained with mono-drug formulations. When simultaneous use is required, co-administration of IVM and FIP is preferable to combined pour-on formulations because IVM absorption is better as injectable than in topical administration.
EEA Rafaela
Fil: Sarli, Macarena. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela. Instituto de Investigación de la Cadena Láctea (IDICAL); Argentina
Fil: Sarli, Macarena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación de la Cadena Láctea (IDICAL); Argentina
Fil: Rossner, Maria Victoria. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Colonia Benitez; Argentina
Fil: Torrents, Jorgelina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela. Instituto de Investigación de la Cadena Láctea (IDICAL); Argentina
Fil: Torrents, Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación de la Cadena Láctea (IDICAL); Argentina
Fil: Miró, V. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Centro de Investigación Veterinaria de Tandil (CIVETAN). Laboratorio de Farmacología; Argentina.
Fil: Miró, V. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación Veterinaria de Tandil (CIVETAN); Argentina
Fil: Lifschitz, Adrian. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Centro de Investigación Veterinaria de Tandil (CIVETAN). Laboratorio de Farmacología; Argentina.
Fil: Lifschitz, Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación Veterinaria de Tandil (CIVETAN); Argentina
Fil: Nava, Santiago. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela. Instituto de Investigación de la Cadena Láctea (IDICAL); Argentina
Fil: Nava, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación de la Cadena Láctea (IDICAL); Argentina
description The objective of this study was to compare the therapeutic and pharmacological performance of ivermectin (IVM) and fipronil (FIP) administered as single drugs, combined in a same formulation, or co-administered individually, as potential strategies to improve treatment efficacy against multi-resistant Rhipicephalus microplus populations. The effect of IVM dose escalation was also evaluated. Naturally infested heifers were allocated into six groups (G) and treated with: injectable IVM 1% at 0.2 mg/kg (G-I) or 0.4 mg/kg (G-II); FIP pour-on at 1 mg/kg (G-III); pour-on formulation of IVM/FIP (0.5 mg/kg IVM + 1 mg/kg FIP; G-IV); co-administration of injectable IVM (0.2 mg/kg) and pour-on FIP (1 mg/kg; G-V); untreated (G-VI). IVM and FIP concentrations in plasma and ticks were quantified by HPLC. Absolute control was not achieved in any treated group. Therapeutic efficacy ranged from 66 to 82.6%, 88.0–97.3%, and 75.7–96.9% at days 3, 7, and 9 post-treatment, respectively, and outlier animals with high tick counts were consistently observed. Although significantly higher plasma IVM concentrations were achieved with the double dose, efficacy was not improved compared with the standard dose. Cattle treated with the pour-on combination showed markedly lower plasma IVM levels due to reduced topical absorption. Co-administration of individual drugs produced pharmacokinetic profiles similar to single-drug treatments. Neither IVM dose escalation nor IVM-FIP combinations improve therapeutic outcomes compared with those obtained with mono-drug formulations. When simultaneous use is required, co-administration of IVM and FIP is preferable to combined pour-on formulations because IVM absorption is better as injectable than in topical administration.
publishDate 2026
dc.date.none.fl_str_mv 2026-07-20T12:10:38Z
2026-07-20T12:10:38Z
2026-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
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info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12123/27070
https://link.springer.com/article/10.1007/s11259-026-11125-3
0165-7380
1573-7446
https://doi.org/10.1007/s11259-026-11125-3
url http://hdl.handle.net/20.500.12123/27070
https://link.springer.com/article/10.1007/s11259-026-11125-3
https://doi.org/10.1007/s11259-026-11125-3
identifier_str_mv 0165-7380
1573-7446
dc.language.none.fl_str_mv eng
language eng
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Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv restrictedAccess
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 Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv Veterinary Research Communications 50 : article number 172. (2026)
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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