RESUMEN
Macrocyclic lactones (MLs) are the cornerstone of parasite control in livestock due to their broad-spectrum activity against endo (nematodes) and ecto (lice, ticks, mites) parasites. These molecules, introduced into the veterinary pharmaceutical market 40 years ago, have substantially improved animal welfare and productivity by offering 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 parasite resistance. This review focuses on the critical link between drug pharmacokinetics (variation in concentration profiles and exposure over time) and pharmacodynamics (drug efficacy) and the ability of both avermectin and milbemycin MLs families to control livestock ectoparasites. This review discusses the integrated assessment of drug behavior in the host, its diffusion into target parasites, and the impact of different pharmaceutical formulations on enhancing drug delivery to infection sites. These are considered critical research/development areas to optimize the use of MLs, preventing treatment failures and finally extending the lifespan of these essential pharmaceutical ingredients. Finally, the importance of the rational use of MLs, guided by parasite epidemiology and pharmacological knowledge, is emphasized as a key strategy to preserve the antiparasitic efficacy of these still very useful molecules.
RESUMEN
Myocoptes musculinus is the most common fur mite identified among laboratory mice; infested mice, in addition to dermatological signs, may also be prone to secondary infections, affecting the outcome of a research trial. This trial was conducted in order to assess the safety and efficacy of a single topical administration of eprinomectin (5mg/kg BW) in a naturally infested laboratory mice colony. A safety trial was conducted on 20 uninfested pregnant females assigned to two groups, receiving eprinomectin and mineral oil, respectively. The mice were examined daily for signs of illness or toxicity; nests were individually weighted at 21 and 28 days postpartum. No acute toxicity was observed, all treated females gave full term delivery and number and mean weight of newborns ranged in the physiological values. To evaluate the efficacy, 20 naturally infested non-pregnant females were divided into two groups, treated as in the safety trial. Animals were observed daily for 15 min until 21 days post-treatment (DPT) and a “pruritus index” (PI: scratching and gnawing acts/mouse/min) was calculated. Pelage examination was performed on DPT 7, 14, 21 and 50. The “PI” was significantly lower in the treated group and mites were eradicated from all infested animals. A single topical administration of eprinomectin at a (high) dosage of 5mg/kg BW was safe and effective to control M. musculinus in mice.
Myocoptes musculinus é o ácaro de pele mais comum identificado entre camundongos de laboratório. Camundongos infestados, além de sinais dermatológicos, também podem ser propensos a infecções secundárias, interferindo no resultado de um ensaio de pesquisa. Este estudo foi realizado para avaliar a segurança e eficácia de uma única administração tópica de eprinomectina (5mg / kg PV) em uma colônia de camundongos de laboratório naturalmente infestada. Um estudo de segurança foi realizado em 20 fêmeas prenhes sadias, divididas em dois grupos, recebendo eprinomectina e óleo mineral, respectivamente. Os camundongos foram examinados diariamente para detectar quaisquer sinais da doença ou toxicidade; camundongos recém-nascidos foram pesados individualmente aos 21 e 28 dias pós-parto. Nenhuma toxicidade aguda foi observada. Todas as fêmeas tratadas chegaram ao parto, o número e peso dos recém-nascidos variaram dentro de parâmetros fisiológicos. Para avaliar a eficácia, 20 camundongos não prenhes, naturalmente infestados, foram divididos em dois grupos: tratado e grupo controle não tratado. Os animais foram observados diariamente durante 15 minutos até os 21 dias pós- tratamento (DPT) e um índice de prurido (IP) - arranhões e ato de roer / camundongo / min) foi calculado. Exame da pelagem foi realizado em DPT 7, 14, 21 e 50. O IP foi significativamente menor no grupo tratado, e os ácaros foram erradicados de todos os animais infestados. Uma única administração tópica de eprinomectina, na dose de 5mg / kg de peso corporal, foi segura e eficaz no controle de M. musculinus em camundongos.