학술논문

The effect of food on the pharmacokinetics of oral ibrutinib in healthy participants and patients with chronic lymphocytic leukemia
Document Type
article
Source
Cancer Chemotherapy and Pharmacology. 75(5)
Subject
Pharmacology and Pharmaceutical Sciences
Biomedical and Clinical Sciences
Clinical Research
Cancer
Rare Diseases
Hematology
Nutrition
Lymphoma
Clinical Trials and Supportive Activities
6.1 Pharmaceuticals
Evaluation of treatments and therapeutic interventions
Metabolic and endocrine
Adenine
Administration
Oral
Adult
Aged
Aged
80 and over
Case-Control Studies
Cross-Over Studies
Fasting
Female
Food-Drug Interactions
Humans
Leukemia
Lymphocytic
Chronic
B-Cell
Male
Middle Aged
Piperidines
Pyrazoles
Pyrimidines
Oncology & Carcinogenesis
Oncology and carcinogenesis
Pharmacology and pharmaceutical sciences
Language
Abstract
PurposeTo assess ibrutinib pharmacokinetics under fasted and fed conditions, impact of food-intake timing, and the safety and tolerability.MethodsThree studies were analyzed. Study 1 was a randomized, open-label, single-dose, four-way crossover study in 44 healthy participants. Study 2 was a randomized, repeat-dose crossover study in 16 patients with previously treated chronic lymphocytic leukemia (CLL). Ibrutinib dose was 420 mg in both studies. Study 3 was an open-label, sequential study to assess the effect of a standard breakfast on ibrutinib 560 mg in eight healthy participants.ResultsAdministration of single-dose ibrutinib under fasting conditions (study 1) resulted in approximately 60 % of exposure compared with drug intake either 30 min before, 30 min after (fed), or 2 h after a high-fat meal. Similar food effect was observed (study 3) when ibrutinib was given 30 min before meal. In CLL patients (study 2), the C max and AUC under fasting conditions were 43 and 61 %, respectively, relative to fed conditions. When administered once-daily in uncontrolled food-intake conditions (≥30 min before or 2 h after), exposures were slightly (≈30 %) lower than in fed condition. When corrected for repeated dosing, pharmacokinetic parameters in healthy participants and patients were comparable. Ibrutinib was generally well tolerated in all settings studied.ConclusionsIbrutinib administered in fasted condition reduces exposure to approximately 60 % as compared with dosing in proximity to food-intake, regardless of timing/type of meal. Because repeated drug intake in fasted condition is unlikely, no food restrictions may be needed to administer ibrutinib.