title: Effect of food or proton pump inhibitor treatment on the bioavailability of dacomitinib in healthy volunteers.
abstract: 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 (AUCinf ) was 114.2% (90%CI, 104.7%-124.5%) and not considered clinically meaningful. In the fasted state, a decrease in dacomitinib AUCinf 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.
authors.affiliation: Pfizer Inc., La Jolla, CA, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Ruiz-Garcia
authors.affiliation: Pfizer Inc., La Jolla, CA, USA.
authors.forename: Joanna C
authors.initials: JC
authors.lastname: Masters
authors.affiliation: Pfizer Clinical Research Unit, Brussels, Belgium.
authors.forename: Laure
authors.initials: L
authors.lastname: Mendes da Costa
authors.affiliation: Pfizer Inc., Groton, CT, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: LaBadie
authors.affiliation: Pfizer Inc., Groton, CT, USA.
authors.forename: Yali
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Pfizer Inc., Groton, CT, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Ni
authors.affiliation: Pfizer Inc., Groton, CT, USA.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Ellery
authors.affiliation: Pfizer Inc., La Jolla, CA, USA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Boutros
authors.affiliation: Pfizer Inc., La Jolla, CA, USA.
authors.forename: Zelanna
authors.initials: Z
authors.lastname: Goldberg
authors.affiliation: Pfizer Inc., New York, NY, USA.
authors.forename: Carlo L
authors.initials: CL
authors.lastname: Bello
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004041:Dietary Fats; D004336:Drug Antagonism; D002149:Energy Intake; D005260:Female; D018565:Food-Drug Interactions; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D052999:Quinazolinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D064750:Rabeprazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D004041:Dietary Fats; D054328:Proton Pump Inhibitors; D052999:Quinazolinones; D064750:Rabeprazole; C525726:dacomitinib
keywords: dacomitinib; drug interaction; food interaction; healthy volunteers; proton pump inhibitor