Erlotinib hydrochloride (V), a quinazoline derived small
molecule inhibitor of epidermal growth factor receptor
(EDGFR) tyrosine kinase, was approved in November,
2004, for the treatment of advanced or metastatic non-smallcell
lung cancer. It belongs to the same class as gefitinib,another quinazoline approved for treatment of advanced lung
cancer, but with improved pharmacokinetic properties. The molecule was originated by Pfizer and development
initiated in collaboration with OSI, which assumed full
rights to the drug when Pfizer merged with Warner Lambert.
Subsequently, Genentech/Roche went into licensing
agreement with OSI to develop and market the drug in the
US and Worldwide.
정의
ChEBI: A quinazoline hydrochloride compound having a (3-ethynylphenyl)amino group at the 4-position and two 2-methoxyethoxy groups at the 6- and 7-positions.
일반 설명
Erlotinib is available as 25-, 100-, and 150-mg tablets fororal administration and is used after failure of first-linetherapy in metastatic NSCLC and as first-line therapy incombination with gemcitabine in the treatment of metastaticpancreatic cancer, and in treating malignant gliomas.The structural similarity to gefitnib imparts similar pharmacokineticbehavior with bioavailability of 60% and proteinbinding of 93%. The agent is extensively metabolizedprimarily by CYP3A4. Three major metabolic pathwayshave been identified, involving oxidative-O-demethylationof the side chains followed by further oxidation to give thecarboxlic acids, oxidation of the acetylene functionalityto give a carboxylic acid, and aromatic hydroxylation ofthe phenyl ring para to the electron-donating nitrogen. Themetabolites are primarily eliminated in the feces, and theterminal half-life is 36 hours.The major toxicities seenwith the agent are dose-limiting skin rash and diarrhea.Other common adverse effects include shortness of breath,fatigue, and nausea.
