Spinosad is a potent inhibitor of canine P-glycoprotein.

Inhibition of the drug transporter P-glycoprotein (P-gp) by the oral flea preventative spinosad has been suggested as the underlying cause of the drug-drug interaction with ivermectin. In this study, an in vitro model consisting of canine cells was validated to describe the inhibitory effect of drugs on canine P-gp. In this model, ivermectin, cyclosporin, verapamil, loperamide and ketoconazole inhibited P-gp function with IC50 values ranging from 0.1 to 3.7 μmol/L. Spinosad was a potent inhibitor of canine P-gp with an IC50 value of 0.27 μmol/L or 0.2 μg/mL. The risk of spinosad causing P-gp related drug-drug interactions in the dog could be predicted by the IC50 value, the oral dosage and plasma concentrations.