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Effect of lapatinib on oral digoxin absorption in patients

Cited 6 time in Web of Science Cited 6 time in Scopus
Authors
Koch, Kevin M.; Smith, Deborah A.; Botbyl, Jeff; Arya, Nikita; Briley, Linda P.; Cartee, Leanne; White, Jane Holshouser; Beyer, Jennifer; Dar, Mohammed M.; Chung, Hyun Choel; Chu, Quincy; Bang, Yung-Jue
Issue Date
2015-11
Citation
Clinical Pharmacology in Drug Development, Vol.4 No.6, pp.449-453
Keywords
lapatinibdigoxindrug interactionp-glycoproteinABCB1
Abstract
The potential for an interaction between lapatinib and absorption of the P-glycoprotein (ABCB1) substrate digoxin at a therapeutic dose in breast cancer patients was characterized. Seventeen women with HER2-positive metastatic breast cancer received a single oral 0.5-mg dose of digoxin on days 1 and 9 and oral lapatinib 1500 mg once daily on days 2 through 9. Digoxin pharmacokinetic parameters were determined on day 1 (digoxin administration alone) and on day 9 (coadministration of lapatinib and digoxin), and parameters were compared to determine the effects of lapatinib on digoxin absorption. Concomitant medications that could affect ABCB1 were accounted for. Lapatinib 1500 mg/day increased digoxin absorption approximately 80%, implicating lapatinib inhibition of intestinal ABCB1-mediated efflux. In summary, coadministration of lapatinib with narrow therapeutic index drugs that are substrates of ABCB1 should be undertaken with caution and dose adjustment should be considered.
ISSN
2160-763X
URI
https://hdl.handle.net/10371/173053
DOI
https://doi.org/10.1002/cpdd.189
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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