The effects of a high-fat meal on single-dose vemurafenib pharmacokinetics

J Clin Pharmacol. 2014 Apr;54(4):368-74. doi: 10.1002/jcph.255. Epub 2014 Jan 22.


Vemurafenib is an orally bioavailable BRAF inhibitor approved for the treatment of BRAF(V600) -mutant metastatic melanoma. It is important to understand the effects of a high-fat meal on the pharmacokinetics (PK) of vemurafenib in humans because it is a Biopharmaceutics Classification System Class IV drug and its PK can be altered by food. An open-label, multicenter, randomized, 2-period crossover study was performed to evaluate the effect of food (high-fat meal) on the PK of a single oral dose of vemurafenib. Secondary objectives were safety and tolerability, efficacy with best overall response rate, and overall survival during the treatment period. The concomitant intake of food (high-fat meal) increased mean Cmax 3.5 to 7.5 µg/mL and mean AUC0-∞ 119 to 360 µg·h/mL after a single 960 mg dose of vemurafenib (N = 13-15 patients). An effect of food on single-dose exposure is suggested by point estimates and 90% CI of geometric mean ratios for vemurafenib plasma AUC0-∞ (4.7) and Cmax (2.5). Toxicity and response rate of vemurafenib in this study were consistent with prior experience in patients with BRAF(V600) -mutant metastatic melanoma. A high-fat meal increased the exposure to vemurafenib without altering the mean terminal half-life.

Keywords: BRAF inhibitor; food effects; high-fat meal; pharmacokinetics; vemurafenib.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacokinetics*
  • Area Under Curve
  • Cross-Over Studies
  • Dietary Fats / pharmacokinetics*
  • Female
  • Food-Drug Interactions*
  • Humans
  • Indoles / adverse effects
  • Indoles / blood
  • Indoles / pharmacokinetics*
  • Male
  • Melanoma / drug therapy
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Middle Aged
  • Mutation
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / blood
  • Protein Kinase Inhibitors / pharmacokinetics*
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf / genetics
  • Sulfonamides / adverse effects
  • Sulfonamides / blood
  • Sulfonamides / pharmacokinetics*
  • Vemurafenib


  • Antineoplastic Agents
  • Dietary Fats
  • Indoles
  • Protein Kinase Inhibitors
  • Sulfonamides
  • Vemurafenib
  • Proto-Oncogene Proteins B-raf