期刊
VETERINARY JOURNAL
卷 200, 期 1, 页码 195-196出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.tvjl.2014.01.012
关键词
ABCB1; Dog; Drug interactions; P-glycoprotein; Ivermectin
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 mu mol/L. Spinosad was a potent inhibitor of canine P-gp with an IC50 value of 0.27 mu mol/L or 0.2 mu g/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. (C) 2014 Elsevier Ltd. All rights reserved.
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