Effect of lapatinib on oral digoxin absorption in patients

Kevin M. Koch, Deborah A. Smith, Jeff Botbyl, Nikita Arya, Linda P. Briley, Leanne Cartee, Jane Holshouser White, Jennifer Beyer, Mohammed M. Dar, Hyun Choel Chung, Quincy Chu, Yung Jue Bang

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4 Citations (Scopus)

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 1500mg/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.

Original languageEnglish
Pages (from-to)449-453
Number of pages5
JournalClinical Pharmacology in Drug Development
Volume4
Issue number6
DOIs
Publication statusPublished - 2015 Nov 1

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science
  • Pharmacology (medical)

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    Koch, K. M., Smith, D. A., Botbyl, J., Arya, N., Briley, L. P., Cartee, L., White, J. H., Beyer, J., Dar, M. M., Chung, H. C., Chu, Q., & Bang, Y. J. (2015). Effect of lapatinib on oral digoxin absorption in patients. Clinical Pharmacology in Drug Development, 4(6), 449-453. https://doi.org/10.1002/cpdd.189