title: Spinosad is a potent inhibitor of canine P-glycoprotein.
abstract: 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.
authors.affiliation: Utrecht University, Institute for Risk Assessment Sciences, Faculty of Veterinary Medicine, Veterinary Pharmacology, Pharmacotherapy and Toxicology, Yalelaan 104, 3584 CM, Utrecht, The Netherlands. Electronic address: j.a.schrickx@uu.nl.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Schrickx
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D004285:Dogs / Q000378:metabolism*; D004338:Drug Combinations; D004347:Drug Interactions; D020128:Inhibitory Concentration 50; D007559:Ivermectin / Q000378:metabolism*; D018942:Macrolides / Q000097:blood / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004338:Drug Combinations; D018942:Macrolides; D004364:Pharmaceutical Preparations; D007559:Ivermectin; C415329:spinosad
keywords: ABCB1; Dog; Drug interactions; Ivermectin; P-glycoprotein