Integrated pharmacokinetic–pharmacodynamic analysis of macrocyclic lactones in sheep infested with resistant Psoroptes ovis

Autores
Herrera, Rodolfo; Miró, Maria Victoria; Lifschitz, Adrian Luis; Larroza, Marcela Patricia
Año de publicación
2026
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The current study aimed to investigate the pharmacokinetic/pharmacodynamic (PK/PD) relationship of five macrocyclic lactone (MLs) formulations, three 1 % formulations (ivermectin, doramectin and moxidectin) and two long-acting 3.15 % products (ivermectin and doramectin), against sheep experimentally infested with resistant Psoroptes ovis under standardized doses. Thirty naïve Merino sheep were experimentally infested and randomly assigned to five treatment groups (n = 6). Baseline mite counts were not used to block animals during group allocation. The three 1 % formulations of ivermectin (IVM), doramectin (DRM), and moxidectin (MXD), were administered off-label at a dose of 0.5–0.6 mg/kg on days 0 and 7, subcutaneously. The long-acting 3.15 % formulations were subcutaneously administered once at their approved doses of 1.05 mg/kg (IVM 3.15 %) and 1.26 mg/kg (DRM 3.15 %). Plasma drug concentrations and mite counts were assessed between 0 and 35 days post-treatment. Conventional 1 % formulations produced higher peak plasma concentrations than long-acting formulations, although the latter showed greater persistence, similar to that observed with repeated MXD 1 %. DRM 1 % showed greater systemic exposure compared to 3.15 % long acting formulations and IVM 1 %. Significant reductions in mite counts were observed by day 7 with DRM 1 %, and by day 14 with IVM 1 % and MXD 1 %. In contrast, long-acting formulations showed delayed responses, with significant reductions only by day 21. Only DRM 1 % and MXD 1 % achieved 100 % efficacy. PK/PD indices established for ML-resistant P. ovis were calculated as the ratio between peak plasma concentration (Cmax) and the minimal inhibitory concentration (MIC) values of 15 and 30 ng/mL (Cmax/MIC), as well as the ratios between the area under the concentration–time curve (AUC) and the same MIC values (AUC/MIC). The Cmax/MIC ratio observed for 1 % formulations were significantly higher compared to those obtained with the long-acting formulations at both MIC levels. For the AUC/MIC parameter, the 1 % formulations exhibited significantly higher values compared to the long-acting formulations for the MIC 30 ng/mL.These findings suggest that both the magnitude and duration of MLs in plasma are critical for efficacy against P. ovis.
EEA Bariloche
Fil: Herrera, Rodolfo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Grupo de Sanidad Animal; Argentina
Fil: Miró, María Victoria. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Centro de Investigación Veterinaria de Tandil (CIVETAN); Argentina.
Fil: Miró, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación Veterinaria de Tandil (CIVETAN); Argentina
Fil: Miró, María Victoria. Provincia de Buenos Aires. Comisión de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; 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); Argentina.
Fil: Lifschitz, Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación Veterinaria de Tandil (CIVETAN); Argentina
Fil: Lifschitz, Adrian. Provincia de Buenos Aires. Comisión de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Larroza, Marcela Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Grupo de Sanidad Animal; Argentina
Fuente
Veterinary Parasitology 342 : 110681. (February 2026)
Materia
Ovinos
Enfermedades de los Animales
Lactona
Farmacocinética
Farmacodinámica
Ivermectina
Sheep
Animal Diseases
Psoroptes ovis
Lactones
Pharmacokinetics
Pharmacodynamics
Ivermectin
Doramectina
Doramectin
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:20.500.12123/24964
Acceder
id INTADig_821f1090ab1b8b357b4620e998fa9a97
oai_identifier_str oai:localhost:20.500.12123/24964
network_acronym_str INTADig
repository_id_str l
network_name_str INTA Digital (INTA)
spelling Integrated pharmacokinetic–pharmacodynamic analysis of macrocyclic lactones in sheep infested with resistant Psoroptes ovisHerrera, RodolfoMiró, Maria VictoriaLifschitz, Adrian LuisLarroza, Marcela PatriciaOvinosEnfermedades de los AnimalesLactonaFarmacocinéticaFarmacodinámicaIvermectinaSheepAnimal DiseasesPsoroptes ovisLactonesPharmacokineticsPharmacodynamicsIvermectinDoramectinaDoramectinThe current study aimed to investigate the pharmacokinetic/pharmacodynamic (PK/PD) relationship of five macrocyclic lactone (MLs) formulations, three 1 % formulations (ivermectin, doramectin and moxidectin) and two long-acting 3.15 % products (ivermectin and doramectin), against sheep experimentally infested with resistant Psoroptes ovis under standardized doses. Thirty naïve Merino sheep were experimentally infested and randomly assigned to five treatment groups (n = 6). Baseline mite counts were not used to block animals during group allocation. The three 1 % formulations of ivermectin (IVM), doramectin (DRM), and moxidectin (MXD), were administered off-label at a dose of 0.5–0.6 mg/kg on days 0 and 7, subcutaneously. The long-acting 3.15 % formulations were subcutaneously administered once at their approved doses of 1.05 mg/kg (IVM 3.15 %) and 1.26 mg/kg (DRM 3.15 %). Plasma drug concentrations and mite counts were assessed between 0 and 35 days post-treatment. Conventional 1 % formulations produced higher peak plasma concentrations than long-acting formulations, although the latter showed greater persistence, similar to that observed with repeated MXD 1 %. DRM 1 % showed greater systemic exposure compared to 3.15 % long acting formulations and IVM 1 %. Significant reductions in mite counts were observed by day 7 with DRM 1 %, and by day 14 with IVM 1 % and MXD 1 %. In contrast, long-acting formulations showed delayed responses, with significant reductions only by day 21. Only DRM 1 % and MXD 1 % achieved 100 % efficacy. PK/PD indices established for ML-resistant P. ovis were calculated as the ratio between peak plasma concentration (Cmax) and the minimal inhibitory concentration (MIC) values of 15 and 30 ng/mL (Cmax/MIC), as well as the ratios between the area under the concentration–time curve (AUC) and the same MIC values (AUC/MIC). The Cmax/MIC ratio observed for 1 % formulations were significantly higher compared to those obtained with the long-acting formulations at both MIC levels. For the AUC/MIC parameter, the 1 % formulations exhibited significantly higher values compared to the long-acting formulations for the MIC 30 ng/mL.These findings suggest that both the magnitude and duration of MLs in plasma are critical for efficacy against P. ovis.EEA BarilocheFil: Herrera, Rodolfo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Grupo de Sanidad Animal; ArgentinaFil: Miró, María Victoria. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Centro de Investigación Veterinaria de Tandil (CIVETAN); Argentina.Fil: Miró, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación Veterinaria de Tandil (CIVETAN); ArgentinaFil: Miró, María Victoria. Provincia de Buenos Aires. Comisión de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Lifschitz, Adrian. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Centro de Investigación Veterinaria de Tandil (CIVETAN); Argentina.Fil: Lifschitz, Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación Veterinaria de Tandil (CIVETAN); ArgentinaFil: Lifschitz, Adrian. Provincia de Buenos Aires. Comisión de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Larroza, Marcela Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Grupo de Sanidad Animal; ArgentinaElsevier2026-01-09T13:26:12Z2026-01-09T13:26:12Z2026-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/24964https://www.sciencedirect.com/science/article/abs/pii/S03044017250029240304-40171873-2550https://doi.org/10.1016/j.vetpar.2025.110681Veterinary Parasitology 342 : 110681. (February 2026)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repograntAgreement/INTA/2023-PD-L06-I115, Resistencia Antimicrobiana y desarrollo de alternativas que minimicen el uso de antibióticos y antiparasitarios para una produccion animal mas sustentableinfo: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)2026-02-05T12:54:26Zoai:localhost:20.500.12123/24964instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2026-02-05 12:54:27.273INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Integrated pharmacokinetic–pharmacodynamic analysis of macrocyclic lactones in sheep infested with resistant Psoroptes ovis
title Integrated pharmacokinetic–pharmacodynamic analysis of macrocyclic lactones in sheep infested with resistant Psoroptes ovis
spellingShingle Integrated pharmacokinetic–pharmacodynamic analysis of macrocyclic lactones in sheep infested with resistant Psoroptes ovis
Herrera, Rodolfo
Ovinos
Enfermedades de los Animales
Lactona
Farmacocinética
Farmacodinámica
Ivermectina
Sheep
Animal Diseases
Psoroptes ovis
Lactones
Pharmacokinetics
Pharmacodynamics
Ivermectin
Doramectina
Doramectin
title_short Integrated pharmacokinetic–pharmacodynamic analysis of macrocyclic lactones in sheep infested with resistant Psoroptes ovis
title_full Integrated pharmacokinetic–pharmacodynamic analysis of macrocyclic lactones in sheep infested with resistant Psoroptes ovis
title_fullStr Integrated pharmacokinetic–pharmacodynamic analysis of macrocyclic lactones in sheep infested with resistant Psoroptes ovis
title_full_unstemmed Integrated pharmacokinetic–pharmacodynamic analysis of macrocyclic lactones in sheep infested with resistant Psoroptes ovis
title_sort Integrated pharmacokinetic–pharmacodynamic analysis of macrocyclic lactones in sheep infested with resistant Psoroptes ovis
dc.creator.none.fl_str_mv Herrera, Rodolfo
Miró, Maria Victoria
Lifschitz, Adrian Luis
Larroza, Marcela Patricia
author Herrera, Rodolfo
author_facet Herrera, Rodolfo
Miró, Maria Victoria
Lifschitz, Adrian Luis
Larroza, Marcela Patricia
author_role author
author2 Miró, Maria Victoria
Lifschitz, Adrian Luis
Larroza, Marcela Patricia
author2_role author
author
author
dc.subject.none.fl_str_mv Ovinos
Enfermedades de los Animales
Lactona
Farmacocinética
Farmacodinámica
Ivermectina
Sheep
Animal Diseases
Psoroptes ovis
Lactones
Pharmacokinetics
Pharmacodynamics
Ivermectin
Doramectina
Doramectin
topic Ovinos
Enfermedades de los Animales
Lactona
Farmacocinética
Farmacodinámica
Ivermectina
Sheep
Animal Diseases
Psoroptes ovis
Lactones
Pharmacokinetics
Pharmacodynamics
Ivermectin
Doramectina
Doramectin
dc.description.none.fl_txt_mv The current study aimed to investigate the pharmacokinetic/pharmacodynamic (PK/PD) relationship of five macrocyclic lactone (MLs) formulations, three 1 % formulations (ivermectin, doramectin and moxidectin) and two long-acting 3.15 % products (ivermectin and doramectin), against sheep experimentally infested with resistant Psoroptes ovis under standardized doses. Thirty naïve Merino sheep were experimentally infested and randomly assigned to five treatment groups (n = 6). Baseline mite counts were not used to block animals during group allocation. The three 1 % formulations of ivermectin (IVM), doramectin (DRM), and moxidectin (MXD), were administered off-label at a dose of 0.5–0.6 mg/kg on days 0 and 7, subcutaneously. The long-acting 3.15 % formulations were subcutaneously administered once at their approved doses of 1.05 mg/kg (IVM 3.15 %) and 1.26 mg/kg (DRM 3.15 %). Plasma drug concentrations and mite counts were assessed between 0 and 35 days post-treatment. Conventional 1 % formulations produced higher peak plasma concentrations than long-acting formulations, although the latter showed greater persistence, similar to that observed with repeated MXD 1 %. DRM 1 % showed greater systemic exposure compared to 3.15 % long acting formulations and IVM 1 %. Significant reductions in mite counts were observed by day 7 with DRM 1 %, and by day 14 with IVM 1 % and MXD 1 %. In contrast, long-acting formulations showed delayed responses, with significant reductions only by day 21. Only DRM 1 % and MXD 1 % achieved 100 % efficacy. PK/PD indices established for ML-resistant P. ovis were calculated as the ratio between peak plasma concentration (Cmax) and the minimal inhibitory concentration (MIC) values of 15 and 30 ng/mL (Cmax/MIC), as well as the ratios between the area under the concentration–time curve (AUC) and the same MIC values (AUC/MIC). The Cmax/MIC ratio observed for 1 % formulations were significantly higher compared to those obtained with the long-acting formulations at both MIC levels. For the AUC/MIC parameter, the 1 % formulations exhibited significantly higher values compared to the long-acting formulations for the MIC 30 ng/mL.These findings suggest that both the magnitude and duration of MLs in plasma are critical for efficacy against P. ovis.
EEA Bariloche
Fil: Herrera, Rodolfo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Grupo de Sanidad Animal; Argentina
Fil: Miró, María Victoria. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Centro de Investigación Veterinaria de Tandil (CIVETAN); Argentina.
Fil: Miró, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación Veterinaria de Tandil (CIVETAN); Argentina
Fil: Miró, María Victoria. Provincia de Buenos Aires. Comisión de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; 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); Argentina.
Fil: Lifschitz, Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación Veterinaria de Tandil (CIVETAN); Argentina
Fil: Lifschitz, Adrian. Provincia de Buenos Aires. Comisión de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Larroza, Marcela Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Grupo de Sanidad Animal; Argentina
description The current study aimed to investigate the pharmacokinetic/pharmacodynamic (PK/PD) relationship of five macrocyclic lactone (MLs) formulations, three 1 % formulations (ivermectin, doramectin and moxidectin) and two long-acting 3.15 % products (ivermectin and doramectin), against sheep experimentally infested with resistant Psoroptes ovis under standardized doses. Thirty naïve Merino sheep were experimentally infested and randomly assigned to five treatment groups (n = 6). Baseline mite counts were not used to block animals during group allocation. The three 1 % formulations of ivermectin (IVM), doramectin (DRM), and moxidectin (MXD), were administered off-label at a dose of 0.5–0.6 mg/kg on days 0 and 7, subcutaneously. The long-acting 3.15 % formulations were subcutaneously administered once at their approved doses of 1.05 mg/kg (IVM 3.15 %) and 1.26 mg/kg (DRM 3.15 %). Plasma drug concentrations and mite counts were assessed between 0 and 35 days post-treatment. Conventional 1 % formulations produced higher peak plasma concentrations than long-acting formulations, although the latter showed greater persistence, similar to that observed with repeated MXD 1 %. DRM 1 % showed greater systemic exposure compared to 3.15 % long acting formulations and IVM 1 %. Significant reductions in mite counts were observed by day 7 with DRM 1 %, and by day 14 with IVM 1 % and MXD 1 %. In contrast, long-acting formulations showed delayed responses, with significant reductions only by day 21. Only DRM 1 % and MXD 1 % achieved 100 % efficacy. PK/PD indices established for ML-resistant P. ovis were calculated as the ratio between peak plasma concentration (Cmax) and the minimal inhibitory concentration (MIC) values of 15 and 30 ng/mL (Cmax/MIC), as well as the ratios between the area under the concentration–time curve (AUC) and the same MIC values (AUC/MIC). The Cmax/MIC ratio observed for 1 % formulations were significantly higher compared to those obtained with the long-acting formulations at both MIC levels. For the AUC/MIC parameter, the 1 % formulations exhibited significantly higher values compared to the long-acting formulations for the MIC 30 ng/mL.These findings suggest that both the magnitude and duration of MLs in plasma are critical for efficacy against P. ovis.
publishDate 2026
dc.date.none.fl_str_mv 2026-01-09T13:26:12Z
2026-01-09T13:26:12Z
2026-02
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/20.500.12123/24964
https://www.sciencedirect.com/science/article/abs/pii/S0304401725002924
0304-4017
1873-2550
https://doi.org/10.1016/j.vetpar.2025.110681
url http://hdl.handle.net/20.500.12123/24964
https://www.sciencedirect.com/science/article/abs/pii/S0304401725002924
https://doi.org/10.1016/j.vetpar.2025.110681
identifier_str_mv 0304-4017
1873-2550
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repograntAgreement/INTA/2023-PD-L06-I115, Resistencia Antimicrobiana y desarrollo de alternativas que minimicen el uso de antibióticos y antiparasitarios para una produccion animal mas sustentable
dc.rights.none.fl_str_mv info:eu-repo/semantics/restrictedAccess
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 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 Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Veterinary Parasitology 342 : 110681. (February 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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