Clinical Pharmacokinetics of Vemurafenib.
Clin Pharmacokinet
; 56(9): 1033-1043, 2017 09.
Article
en En
| MEDLINE
| ID: mdl-28255850
ABSTRACT
Vemurafenib is an orally administered small-molecule inhibitor of the oncogenic BRAF kinase that is indicated for the treatment of patients with unresectable or metastatic melanoma harbouring BRAF V600 mutations. Vemurafenib is absorbed rapidly after a single oral dose of 960 mg, reaching maximum drug concentration approximately 4 h after administration. Extensive accumulation occurs after multiple dosing at 960 mg twice daily. Steady state is achieved after approximately 15-21 days and exposure at steady state is relatively constant. Population pharmacokinetic analysis identified a vemurafenib half-life of ≈57 h and elimination appears to be predominantly via the hepatic route. Pharmacokinetic parameters are generally consistent regardless of age, sex or race. No dose adjustments are necessary for patients with mild or moderate hepatic or renal impairment, but the effects of severe hepatic or renal impairment on vemurafenib pharmacokinetics are uncertain. Vemurafenib appears to be a substrate and inducer of cytochrome P450 (CYP) 3A4, a moderate inhibitor of CYP1A2 and both a substrate and inhibitor of the drug efflux transporters P-glycoprotein and breast cancer resistance protein. The relationship between plasma vemurafenib concentrations and response remains to be clarified.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Sulfonamidas
/
Inhibidores de Proteínas Quinasas
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Inductores del Citocromo P-450 CYP3A
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Inhibidores del Citocromo P-450 CYP1A2
/
Indoles
/
Antineoplásicos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Clin Pharmacokinet
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos