Toxicology of avermectins and milbemycins (macrocylic lactones) and the role of P-glycoprotein in dogs and cats

The macrocyclic lactones (MLs) are parasiticides able to kill a wide variety of arthropods and nematodes. They have a high margin of safety for labeled indications, and ivermectin has become the best-selling antiparasitic in the world. Dogs of certain breeds and mixtures of those breeds have a defect in the ABCB1 gene (formerly MDR1 gene) that results in a lack of functional P-glycoprotein, which leads to accumulation of the MLs in the central nervous system and a higher risk of adverse effects when exposed. There is no specific antidote for ML toxicosis so the most important part of treatment is good supportive care.