P-glycoprotein-mediated renal tubular secretion of digoxin: the toxicological significance of the urine-blood barrier model.
We provide direct evidence that verapamil inhibits active digoxin secretion in renal tubular cells (LLC-PK1), and that verapamil increases cellular accumulation of digoxin. These findings suggest that verapamil inhibits the digoxin active secretory transport at the apical membranes, supporting the theory that P-glycoprotein mediates digoxin secretion in the renal tubular cells. Based on existing data on digoxin transport, we present a hypothetical model for the renal handling of digoxin, implying that P-glycoprotein functions as a driving mechanism of a unidirectional "urine-blood" barrier.
Ito
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S
Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.
Woodland
C
C
Harper
P A
PA
Koren
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G
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000704:Analysis of Variance; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D002460:Cell Line; D004077:Digoxin / Q000493:pharmacokinetics*; D007684:Kidney Tubules / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D008954:Models, Biological; D013552:Swine; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D004077:Digoxin; D014700:Verapamil