title: The effects of a high-fat meal on single-dose vemurafenib pharmacokinetics.
abstract: 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.
authors.affiliation: Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA.
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
authors.forename: Weijiang
authors.initials: W
authors.lastname: Zhang
authors.forename: Ilsung
authors.initials: I
authors.lastname: Chang
authors.forename: Keisuke
authors.initials: K
authors.lastname: Shirai
authors.forename: Marc S
authors.initials: MS
authors.lastname: Ernstoff
authors.forename: Adil
authors.initials: A
authors.lastname: Daud
authors.forename: C Lance
authors.initials: CL
authors.lastname: Cowey
authors.forename: Gregory
authors.initials: G
authors.lastname: Daniels
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Seja
authors.forename: Elizabeth
authors.initials: E
authors.lastname: O'Laco
authors.forename: John A
authors.initials: JA
authors.lastname: Glaspy
authors.forename: Bartosz
authors.initials: B
authors.lastname: Chmielowski
authors.forename: Todd
authors.initials: T
authors.lastname: Hill
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Joe
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Grippo
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000493:pharmacokinetics*; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics; D013449:Sulfonamides / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; D004041:Dietary Fats; D007211:Indoles; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF inhibitor; food effects; high-fat meal; pharmacokinetics; vemurafenib