The mechanism of the verapamil-digoxin interaction in renal tubular cells (LLC-PK1).
Verapamil, usually given as a racemic mixture, decreases in vivo and in vitro digoxin renal tubular secretion, which is suggested to be mediated by P-glycoprotein, an ATP-dependent multidrug efflux pump. Importantly, the two enantiomers of verapamil have been reported to similarly inhibit P-glycoprotein-mediated transport of chemotherapeutic agents. In this study, we examined effects of enantiomers of verapamil on digoxin transport across an LLC-PK1 cell monolayer, a model of proximal renal tubular cells. The results indicate that verapamil inhibition of digoxin transport is non-stereospecific. Furthermore, the verapamil-digoxin interaction is not competitive. The two drugs may not share a common initial step in the P-glycoprotein-mediated transport.
Ito
S
S
Department of Pediatrics, Hospital for Sick Children, Ontario, Canada.
Woodland
C
C
Harper
P A
PA
Koren
G
G
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004077:Digoxin / Q000493:pharmacokinetics*; D004347:Drug Interactions; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism; D013552:Swine; D014700:Verapamil / Q000494:pharmacology*
D004077:Digoxin; D014700:Verapamil