A functional model for feline P-glycoprotein.

Abstract

P-gp (ABCB1) belongs to the group of export transporters that is expressed in various species at biological barriers. Inhibition of P-gp can lead to changes in pharmacokinetics of drugs (drug-drug interactions), which can lead to toxicity and adverse side effects. This study aimed to establish a functional assay to measure the inhibitory potential of veterinary drugs on feline P-gp by means of fluorescence-associated flow cytometry of feline lymphoma cells. In this model, PSC833 and ivermectin potently inhibited P-gp function; cyclosporine and verapamil moderately inhibited P-gp function, whereas ketoconazole, itraconazole, diazepam, and its metabolites had no effect on P-gp function. This model can be used for testing the inhibitory potency of (new) drugs on feline P-gp.