Macrocyclic lactones and ectoparasites control in livestock: Efficacy, drug resistance and therapeutic challenges

Abstract

Macrocyclic lactones (MLs) are the cornerstone of parasite control in livestock due to their broad-spectrumactivity against endo (nematodes) and ecto (lice, ticks, mites) parasites. These molecules, introduced into theveterinary pharmaceutical market 40 years ago, have substantially improved animal welfare and productivity byoffering extended high efficacy, reducing treatment frequency, and displaying a favorable safety profile. However,their widespread and intensive use has led to a significant challenge nowadays: the development of parasiteresistance. This review focuses on the critical link between drug pharmacokinetics (variation in concentrationprofiles and exposure over time) and pharmacodynamics (drug efficacy) and the ability of both avermectin andmilbemycin MLs families to control livestock ectoparasites. This review discusses the integrated assessment ofdrug behavior in the host, its diffusion into target parasites, and the impact of different pharmaceutical formulationson enhancing drug delivery to infection sites. These are considered critical research/developmentareas to optimize the use of MLs, preventing treatment failures and finally extending the lifespan of theseessential pharmaceutical ingredients. Finally, the importance of the rational use of MLs, guided by parasiteepidemiology and pharmacological knowledge, is emphasized as a key strategy to preserve the antiparasiticefficacy of these still very useful molecules.