The effects of a high-fat meal on single-dose vemurafenib pharmacokinetics.
J Clin Pharmacol
; 54(4): 368-74, 2014 Apr.
Article
em En
| MEDLINE
| ID: mdl-24374975
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
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Gorduras na Dieta
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Interações Alimento-Droga
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Inibidores de Proteínas Quinases
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Indóis
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Melanoma
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Antineoplásicos
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article