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Effects of Esomeprazole on the Pharmacokinetics of Lapatinib in Breast Cancer Patients
Author(s) -
Koch Kevin M.,
Im YoungHyuck,
Kim SungBae,
Urruticoechea Ribate Ander,
Stephenson Joe,
Botbyl Jeffrey,
Cartee Leanne,
Holshouser Jane,
Ridgway Derry
Publication year - 2013
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.45
Subject(s) - lapatinib , esomeprazole , medicine , pharmacokinetics , bioavailability , bedtime , pharmacology , dosing , breast cancer , morning , cancer , gastroenterology , trastuzumab
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.