Effect of food or proton pump inhibitor treatment on the bioavailability of dacomitinib in healthy volunteers.
J Clin Pharmacol
; 56(2): 223-30, 2016 02.
Article
em En
| MEDLINE
| ID: mdl-26179237
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interações Alimento-Droga
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Antagonismo de Drogas
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Quinazolinonas
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Rabeprazol
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article