Clinical Pharmacokinetics of Vemurafenib.

Article Details

Citation

Zhang W, Heinzmann D, Grippo JF

Clinical Pharmacokinetics of Vemurafenib.

Clin Pharmacokinet. 2017 Mar 2. doi: 10.1007/s40262-017-0523-7.

PubMed ID
28255850 [ View in PubMed
]
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 approximately 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.

DrugBank Data that Cites this Article

Drugs
Drug Interactions
DrugsInteraction
Acenocoumarol
Vemurafenib
The serum concentration of Acenocoumarol can be increased when it is combined with Vemurafenib.
Acetaminophen
Vemurafenib
The serum concentration of Acetaminophen can be increased when it is combined with Vemurafenib.
Acyclovir
Vemurafenib
The serum concentration of Acyclovir can be increased when it is combined with Vemurafenib.
Afatinib
Vemurafenib
The serum concentration of Afatinib can be increased when it is combined with Vemurafenib.
Agomelatine
Vemurafenib
The serum concentration of Agomelatine can be increased when it is combined with Vemurafenib.