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Effect of food or proton pump inhibitor treatment on the bioavailability of dacomitinib in healthy volunteers
Author(s) -
RuizGarcia Ana,
Masters Joanna C.,
Mendes da Costa Laure,
LaBadie Robert R.,
Liang Yali,
Ni Grace,
Ellery Craig A.,
Boutros Tanya,
Goldberg Zelanna,
Bello Carlo L.
Publication year - 2016
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.588
Subject(s) - rabeprazole , bioavailability , pharmacology , crossover study , pharmacokinetics , proton pump inhibitor , medicine , washout , meal , placebo , alternative medicine , pathology
This phase 1, open‐label crossover study evaluated the relative bioavailability of dacomitinib in healthy volunteers under fed and fasted conditions and following coadministration with rabeprazole, a potent acid‐reducing proton pump inhibitor (PPI). Twenty‐four male subjects received a single dacomitinib 45‐mg dose under 3 different conditions separated by washout periods of ≥16 days: coadministered with rabeprazole 40 mg under fasting conditions; alone under fasting conditions; and alone after a high‐fat, high‐calorie meal. Increased peak exposure of 23.7% (90% confidence interval [CI], 5.3%–45.2%) was detected with dacomitinib taken after food versus fasting. The adjusted geometric mean ratio (fed/fasted) for area under the plasma concentration−time curve from time zero to infinity (AUC inf ) was 114.2% (90%CI, 104.7%–124.5%) and not considered clinically meaningful. In the fasted state, a decrease in dacomitinib AUC inf was observed following rabeprazole versus dacomitinib alone (PPI+fasted/fasted alone): 71.1% (90%CI, 61.7%–81.8%). Dacomitinib was generally well tolerated. Dacomitinib may be taken with or without food. Use of long‐acting acid‐reducing agents, such as PPIs with dacomitinib should be avoided if possible. Shorter‐acting agents such as antacids and H2‐receptor antagonists may have lesser impact on dacomitinib exposure and may be preferable to PPIs if acid reduction is clinically required.