GEFTINAT吉非替尼片剂说明书全文（中英对照翻译）.doc

For the use only of a Cancer Specialist or a Hospital or an Institution GEFTINAT* (Gefitinib Tablets IP) Composition Each film coated tablet contains: Gefitinib IP 250 mg DESCRIPTION GEFTINAT (gefitinib tablets IP) contain 250 mg of gefitinib IP and are available as reddish brown film-coated tablets engraved with GEFTINAT on one side and 250 on another side tor daily oral administration. Gefitinib is an anilinoquinazoline with the chemical name 4-Quinazolin amine, N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-4-morpholin] propoxy]. It has the molecular formula C22H24C1F4O3,a relative molecular mass of 446.9 and is a white-colored powder. Gefitinib is a free base. CLINICAL PHARMACOLOGY Mechanism of Action: The mechanism of the clinical antitumor action of gefitinib is not fully characterized. Gefitinib inhibits the intracellular phosphorylation of numerous tyrosine kinases associated with transmembrane cell surface receptors, including the tyrosine kinases associated with the epidermal growth factor receptor (EGFRTK). EGFR is expressed on the cell surface of many normal cells and cancer cells. No clinical studies have been performed that demonstrate a correlation between EGFR receptor expression and response to gefitinib. Pharmacokinetics : Gefitinib is absorbed slowly after oral administration with mean bioavailability of 60%. Elimination is by metabolism (primarily CYP3A4) and excretion in feces. The elimination halt-life is about 48 hours. Daily oral administration of gefitinib to cancer patients resulted in a 2- fold accumulation compared to single dose administration. Steady state plasma concentrations are achieved within 10 days. Absorption and Distribution: Gefitinib is slowly absorbed, with peak plasma levels occurring 3-7 hours after dosing and mean oral bioavailability of 60%. Bioavailability is not significantly altered by food. Gefitinib is extensively distributed throughout the body with a mean steady state volume of distribution of 1400L following intraven