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

The Journal of Clinical PharmacologyVolume 54, Issue 4 p. 368-374 Editor's Choice The effects of a high-fat meal on single-dose vemurafenib pharmacokinetics Antoni Ribas MD, PhD, Antoni Ribas MD, PhD Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USASearch for more papers by this authorWeijiang Zhang PhD, Weijiang Zhang PhD F. Hoffman-La Roche, Nutley, NJ, USASearch for more papers by this authorIlsung Chang MD, PhD, Ilsung Chang MD, PhD Genentech, Inc., South San Francisco, CA, USASearch for more papers by this authorKeisuke Shirai MD, Keisuke Shirai MD Medical University of South Carolina, Charleston, SC, USASearch for more papers by this authorMarc S. Ernstoff MD, Marc S. Ernstoff MD Dartmouth Hitchcock Medical Center, Norris Cotton Cancer Center, Lebanon, NH, USASearch for more papers by this authorAdil Daud MBBS, Adil Daud MBBS University of California, San Francisco, CA, USASearch for more papers by this authorC. Lance Cowey MD, C. Lance Cowey MD Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas, TX, USASearch for more papers by this authorGregory Daniels MD, Gregory Daniels MD University of California, San Diego, La Jolla, CA, USASearch for more papers by this authorElizabeth Seja MD, Elizabeth Seja MD Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USASearch for more papers by this authorElizabeth O'Laco, Elizabeth O'Laco Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USASearch for more papers by this authorJohn A. Glaspy MD, John A. Glaspy MD Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USASearch for more papers by this authorBartosz Chmielowski MD, PhD, Bartosz Chmielowski MD, PhD Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USASearch for more papers by this authorTodd Hill MD, MS, Todd Hill MD, MS F. Hoffman-La Roche, Nutley, NJ, USASearch for more papers by this authorAndrew K. Joe MD, Andrew K. Joe MD F. Hoffman-La Roche, Nutley, NJ, USASearch for more papers by this authorJoseph F. Grippo PhD, Corresponding Author Joseph F. Grippo PhD F. Hoffman-La Roche, Nutley, NJ, USA Corresponding Author: Joseph F. Grippo, F. Hoffman-La Roche, 340 Kingsland Street, Nutley, NJ 07110, USA Email: [email protected]Search for more papers by this author Antoni Ribas MD, PhD, Antoni Ribas MD, PhD Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USASearch for more papers by this authorWeijiang Zhang PhD, Weijiang Zhang PhD F. Hoffman-La Roche, Nutley, NJ, USASearch for more papers by this authorIlsung Chang MD, PhD, Ilsung Chang MD, PhD Genentech, Inc., South San Francisco, CA, USASearch for more papers by this authorKeisuke Shirai MD, Keisuke Shirai MD Medical University of South Carolina, Charleston, SC, USASearch for more papers by this authorMarc S. Ernstoff MD, Marc S. Ernstoff MD Dartmouth Hitchcock Medical Center, Norris Cotton Cancer Center, Lebanon, NH, USASearch for more papers by this authorAdil Daud MBBS, Adil Daud MBBS University of California, San Francisco, CA, USASearch for more papers by this authorC. Lance Cowey MD, C. Lance Cowey MD Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas, TX, USASearch for more papers by this authorGregory Daniels MD, Gregory Daniels MD University of California, San Diego, La Jolla, CA, USASearch for more papers by this authorElizabeth Seja MD, Elizabeth Seja MD Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USASearch for more papers by this authorElizabeth O'Laco, Elizabeth O'Laco Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USASearch for more papers by this authorJohn A. Glaspy MD, John A. Glaspy MD Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USASearch for more papers by this authorBartosz Chmielowski MD, PhD, Bartosz Chmielowski MD, PhD Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USASearch for more papers by this authorTodd Hill MD, MS, Todd Hill MD, MS F. Hoffman-La Roche, Nutley, NJ, USASearch for more papers by this authorAndrew K. Joe MD, Andrew K. Joe MD F. Hoffman-La Roche, Nutley, NJ, USASearch for more papers by this authorJoseph F. Grippo PhD, Corresponding Author Joseph F. Grippo PhD F. Hoffman-La Roche, Nutley, NJ, USA Corresponding Author: Joseph F. Grippo, F. Hoffman-La Roche, 340 Kingsland Street, Nutley, NJ 07110, USA Email: [email protected]Search for more papers by this author First published: 28 December 2013 https://doi.org/10.1002/jcph.255Citations: 39 Clinical trial registration number NCT01264380. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract Vemurafenib is an orally bioavailable BRAF inhibitor approved for the treatment of BRAFV600-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 BRAFV600-mutant metastatic melanoma. A high-fat meal increased the exposure to vemurafenib without altering the mean terminal half-life. References 1 Davies H, Bignell GR, Cox C, et al. 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