title: Effect of lapatinib on oral digoxin absorption in patients.
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.
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Koch
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Smith
authors.affiliation: Provonix, Inc., Mullica Hill, NJ, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Botbyl
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Nikita
authors.initials: N
authors.lastname: Arya
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Linda P
authors.initials: LP
authors.lastname: Briley
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Leanne
authors.initials: L
authors.lastname: Cartee
authors.affiliation: ICON Clinical Research, Durham, NC, USA.
authors.forename: Jane Holshouser
authors.initials: JH
authors.lastname: White
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Beyer
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.|Current address: MedImmune, Inc., 35 West Watkins Mill Road, Gaithersburg, MD, 20878, USA.
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Dar
authors.affiliation: Severance Hospital, Clinical Trial Support, Seoul, Korea.
authors.forename: Hyun Choel
authors.initials: HC
authors.lastname: Chung
authors.affiliation: Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: Quincy
authors.initials: Q
authors.lastname: Chu
authors.affiliation: Seoul National University Hospital, Clinical Research Institute, Seoul, Korea.
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000378:metabolism; D000284:Administration, Oral; D000328:Adult; D000416:Alberta; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004077:Digoxin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D065569:Gastrointestinal Absorption / Q000187:drug effects*; D006207:Half-Life; D006801:Humans; D000077341:Lapatinib; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D018570:Risk Assessment; D066106:Seoul
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D002316:Cardiotonic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077341:Lapatinib; D004077:Digoxin
keywords: ABCB1; digoxin; drug interaction; lapatinib; p-glycoprotein