The effect of food on the pharmacokinetics of oral ibrutinib in healthy participants and patients with chronic lymphocytic leukemia

Cancer Chemother Pharmacol. 2015 May;75(5):907-16. doi: 10.1007/s00280-015-2708-9. Epub 2015 Feb 28.


Purpose: To assess ibrutinib pharmacokinetics under fasted and fed conditions, impact of food-intake timing, and the safety and tolerability.

Methods: Three 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.

Results: Administration 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.

Conclusions: Ibrutinib 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.

Trial registration: NCT01105247 NCT01820936 NCT01866033.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cross-Over Studies
  • Fasting / metabolism
  • Female
  • Food-Drug Interactions*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / blood
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism*
  • Male
  • Middle Aged
  • Piperidines
  • Pyrazoles / administration & dosage
  • Pyrazoles / adverse effects
  • Pyrazoles / blood
  • Pyrazoles / pharmacokinetics*
  • Pyrimidines / administration & dosage
  • Pyrimidines / adverse effects
  • Pyrimidines / blood
  • Pyrimidines / pharmacokinetics*


  • Piperidines
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • Adenine

Associated data