Interaction of Avermectins with Human and Canine P-Glycoprotein Transporters

摘要

The transport of the anti-parasitic agents,rnivermectin and selamectin, was studied in humanrnintestinal epithelial cell monolayers and caninernperipheral blood lymphocytes (PBL). Both cell typesrnexpress P-glycoprotein (P-gp). Fluxes of rhodamine-rn123 dye and radiolabelled avermectins showed thatrnivermectin and selamectin behaved similarly inrnintestinal monolayers as potent P-gp substrates andrninhibitors. Both drugs also inhibited the efflux ofrnrhodamine-123 from PBL. These in vitro studiesrnsuggest that differences in safety profiles betweenrnthese avermectins in sensitive canine breeds cannotrnbe explained in terms of P-gp interactions.