Effects of Esomeprazole on the Pharmacokinetics of Lapatinib in Breast Cancer Patients.
The aqueous solubility of lapatinib declines significantly at pH >4, suggesting that its bioavailability might be lowered by acid-reducing drugs. A study was therefore conducted to assess the effects of esomeprazole on lapatinib pharmacokinetics (PK). Women with metastatic human epidermal growth factor receptor 2 positive (HER2(+) ) breast cancer were enrolled. Patients received 1,250 mg lapatinib once daily (QD) in the morning on Days 1-7 (Period 1) and Days 8-14 (Period 2) with 40 mg esomeprazole QD at bedtime 3 hours after dinner on Days 8-14. Lapatinib PK sampling occurred during the 24-hour steady-state dosing intervals on Day 7 (lapatinib alone) and Day 14 (lapatinib with esomeprazole). Esomeprazole treatment resulted in decreased lapatinib bioavailability (mean 26%, range 6-49%) that was inversely associated with patient age as a significant covariate.
GlaxoSmithKline Pharmaceuticals, Clinical Pharmacology Modeling and Simulation, Research Triangle Park, NC, USA.
Kevin M
KM
Koch
Samsung Medical Center, Seoul, Korea.
Young-Hyuck
YH
Im
Asan Medical Center.
Sung-Bae
SB
Kim
Institut Catalá d' Oncología, Hospital Duran i Reynals.
Ander
A
Urruticoechea Ribate
Cancer Centers of the Carolinas.
Joe
J
Stephenson
Provonix, LLC.
Jeffrey
J
Botbyl
GlaxoSmithKline, Oncology Drug Development.
Leanne
L
Cartee
ICON Clinical Research.
Jane
J
Holshouser
GlaxoSmithKline, Oncology Drug Development.
Derry
D
Ridgway
breast cancer; drug interaction; esomeprazole; lapatinib; proton pump inhibitor