A model for the prediction of digoxin-drug interactions at the renal tubular cell level.
Digoxin-drug interactions are relatively common causes of digitalis toxicity. Recently, the clinical importance of the renal tubular secretion of digoxin has been proven by documenting drug interactions at this level. The authors describe a model using cultured renal tubular cell monolayers that can be used to predict drug interactions with the cardiac glycoside. This model accurately documents known clinical digoxin interactions such as those with verapamil and propafenone. The common feature of these interactions is that they involve P-glycoprotein substrates (e.g., digoxin, vincristine, vinblastine) or inhibitors (e.g., quinidine, cyclosporine). In the case of the newly described interaction of digoxin with itraconazole, the model preceded the emergence of clinical cases.
Woodland
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The Department of Pharmacology, The Hospital for Sick Children, The University of Toronto, Ontario, Canada.
Ito
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Koren
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D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D004077:Digoxin / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics*; D004232:Diuretics / Q000493:pharmacokinetics / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D011405:Propafenone / Q000494:pharmacology; D013552:Swine; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000889:Anti-Arrhythmia Agents; D000935:Antifungal Agents; D000972:Antineoplastic Agents, Phytogenic; D002121:Calcium Channel Blockers; D004232:Diuretics; D006727:Hormone Antagonists; D007166:Immunosuppressive Agents; D011405:Propafenone; D004077:Digoxin; D014700:Verapamil