Interaction of Avermectins with Human and Canine P-Glycoprotein Transporters

摘要

The transport of the anti-parasitic agents, ivermectin and selamectin, was studied in human intestinal epithelial cell monolayers and canine peripheral blood lymphocytes (PBL). Both cell types express P-glycoprotein (P-gp). Fluxes of rhodamine- 123 dye and radiolabelled avermectins showed that ivermectin and selamectin behaved similarly in intestinal monolayers as potent P-gp substrates and inhibitors. Both drugs also inhibited the efflux of rhodamine-123 from PBL. These in vitro studies suggest that differences in safety profiles between these avermectins in sensitive canine breeds cannot be explained in terms of P-gp interactions.