english Icono del idioma   español Icono del idioma  

Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12008/40927 How to cite
Title: Caenorhabditis elegans as a valuable model for the study of anthelmintic pharmacodynamics and drug-drug interactions: the case of ivermectin and eprinomectin
Authors: Suárez, Gonzalo
Alcántara, Ignacio
Salinas, Gustavo
Type: Artículo
Descriptors: FARMACOLOGIA, RESISTENCIA ANTIPARASITARIA, PARASITOS, HELMINTOS, NEMATODA
Issue Date: 2022
Abstract: Caenorhabditis elegans is a free-living nematode that has been validated for anthelmintic drug screening. However, this model has not been used to address anthelmintic dose-response-time and drug-drug interactions through matrix array methodology. Eprinomectin (EPM) and Ivermectin (IVM) are macrocyclic lactones widely used as anthelmintics. Despite being very similar, EPM and IVM are combined in commercial formulations or mixed by farmers, under the assumption that the combination would increase their efficacy. However, there is no data reported on the pharmacological evaluation of the combination of both drugs. In this study, we assessed the pharmacodynamics and drug-drug interactions of these two anthelmintic drugs. Since the action of these drugs causes worm paralysis, we used an infrared motility assay to measure EPM and IVM effects on worm movement over time. The results showed that EPM was slightly more potent than IVM, that drug potency increased with drug time exposure, and that once paralyzed, worms did not recover. Different EPM/IVM concentration ratios were used and synergy and combination sensitivity scores were determined at different exposure times, applying Highest Single Agent (HSA), Loewe additivity, Bliss and Zero Interaction Potency (ZIP) models. The results clearly indicate that there is neither synergy nor antagonism between both macrocyclic lactones. This study shows that it is more relevant to prioritize the exposure time of each individual drug than to combine them to improve their effects. The results highlight the utility of C. elegans to address pharmacodynamics studies, particularly for drug-drug interactions. Models in vitro can be integrated to facilitate preclinical and clinical translational studies and help researchers to understand drug-drug interactions and achieve rational therapeutic regimes.
Publisher: Frontiers Media
IN: Frontiers in pharmacology 2022. -- 9 h.
Citation: Suárez, G, Alcántara, I y Salinas, G. "Caenorhabditis elegans as a valuable model for the study of anthelmintic pharmacodynamics and drug-drug interactions: the case of ivermectin and eprinomectin". Frontiers in pharmacology. [en línea] 2022, 9 h. DOI: 10.3389/fphar.2022.984905
License: Licencia Creative Commons Atribución (CC - By 4.0)
Appears in Collections:Publicaciones académicas y científicas - Facultad de Química



This item is licensed under a Creative Commons License Creative Commons