Integrated pharmacokinetic–pharmacodynamic analysis of macrocyclic lactones in sheep infested with resistant Psoroptes ovis
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...
| Autores principales: | , , , |
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| Formato: | info:ar-repo/semantics/artículo |
| Lenguaje: | Inglés |
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Elsevier
2026
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| Materias: | |
| Acceso en línea: | 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 |
| _version_ | 1855039038941036544 |
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| author | Herrera, Rodolfo Miró, Maria Victoria Lifschitz, Adrian Luis Larroza, Marcela Patricia |
| author_browse | Herrera, Rodolfo Larroza, Marcela Patricia Lifschitz, Adrian Luis Miró, Maria Victoria |
| author_facet | Herrera, Rodolfo Miró, Maria Victoria Lifschitz, Adrian Luis Larroza, Marcela Patricia |
| author_sort | Herrera, Rodolfo |
| collection | INTA Digital |
| 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. |
| format | info:ar-repo/semantics/artículo |
| id | INTA24964 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2026 |
| publishDateRange | 2026 |
| publishDateSort | 2026 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| record_format | dspace |
| spelling | INTA249642026-01-09T13:30:52Z Integrated pharmacokinetic–pharmacodynamic analysis of macrocyclic lactones in sheep infested with resistant Psoroptes ovis Herrera, Rodolfo Miró, Maria Victoria Lifschitz, Adrian Luis Larroza, Marcela Patricia Ovinos Enfermedades de los Animales Lactona Farmacocinética Farmacodinámica Ivermectina Sheep Animal Diseases Psoroptes ovis Lactones Pharmacokinetics Pharmacodynamics Ivermectin Doramectina Doramectin 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 2026-01-09T13:26:12Z 2026-01-09T13:26:12Z 2026-02 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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 eng 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 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) application/pdf Elsevier Veterinary Parasitology 342 : 110681. (February 2026) |
| spellingShingle | Ovinos Enfermedades de los Animales Lactona Farmacocinética Farmacodinámica Ivermectina Sheep Animal Diseases Psoroptes ovis Lactones Pharmacokinetics Pharmacodynamics Ivermectin Doramectina Doramectin Herrera, Rodolfo Miró, Maria Victoria Lifschitz, Adrian Luis Larroza, Marcela Patricia 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 |
| 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_short | 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 |
| topic | Ovinos Enfermedades de los Animales Lactona Farmacocinética Farmacodinámica Ivermectina Sheep Animal Diseases Psoroptes ovis Lactones Pharmacokinetics Pharmacodynamics Ivermectin Doramectina Doramectin |
| 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 |
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