Macrocyclic lactones: mechanisms of action

Schematic representation of the main pharmacodynamic features (left) and pharmacokinetic features (right) for macrocyclic lactone antiparasitic compounds. Macrocyclic lactones include avermectins (eg, ivermectin, doramectin, eprinomectin) and milbemycins (moxidectin). They are 16-membered lactones, with high lipophilicity and an extended/potent broad spectrum of ecto- and endoparasitic persistence (endectocide compounds). Extended antiparasitic persistence is based on the following pharmacokinetic properties: depot at the administration site (SC injection), strong adsorption to particulate GI digesta, extensive/reversible plasma/tissue exchange, fat reservoir, low metabolism rate, extensive biliary and P-glycoprotein–mediated intestinal secretion, and large enterohepatic recycling.