威罗菲尼
最大值
药代动力学
医学
交叉研究
餐食
耐受性
药理学
内科学
不利影响
转移性黑色素瘤
癌症
安慰剂
病理
替代医学
作者
Antoni Ribas,Weijiang Zhang,Ilsung Chang,Keisuke Shirai,Marc S. Ernstoff,Adil Daud,C. Lance Cowey,Gregory A. Daniels,Elizabeth Seja,Elizabeth O'Laco,John A. Glaspy,Bartosz Chmielowski,Todd Hill,Andrew K. Joe,Joseph F. Grippo
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI