Ivermectin Toxicokinetics in Rainbow Trout (oncorhynchus Mykiss) Following P-glycoprotein Induction.

Changes to ivermectin (IVM [22,23-dihydro avermectin B1a + 22,23-dihydro avermectin B1b]) toxicokinetics (TK) with and without P-glycoprotein (P-gp) inhibition by cyclosporin A (CsA) were examined in rainbow trout (Oncorhynchus mykiss). Rainbow trout were injected with 175 μg/kg 3H-IVM (8.6 μCi/mg IVM) with or without co-administration of 480 μg/kg CsA into the caudal vasculature. Fish were sacrificed at various time points (0.25, 0.5, 1, 3, 24, 48, 96, and 168 h) for organ and tissue sampling (blood, liver, kidney, gill, intestines, brain [5 regions], eye, gonad, and fat) which were analyzed for IVM-derived radioactivity. The IVM concentration decreased over time in blood, liver, kidney, and gill, while concentrations in other tissues remained constant. The highest maximum IVM concentration (Cmax) was found in kidney, followed by liver; the lowest Cmax was found in eye, followed by brain and adipose tissue. The highest