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QuickView for Gefitinib (compound)

Name: gefitinib
PubChem Compound ID: 11719266
Molecular formula: C22H24ClFN4O3
Molecular weight: 445.905 g/mol
Name: gefitinib
Name (isomeric): DB00317
Drug Type: small molecule
ZD-1839; ZD1839
Brand: Iressa, Tarceva, Irressat
Category: Antineoplastic Agents, Protein Kinase Inhibitors
CAS number: 184475-35-2
Indication: For the continued treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of either platinum-based or docetaxel chemotherapies.
Pharmacology: 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 (EGFR-TK). EGFR is expressed on the cell surface of many normal cells and cancer cells.
Mechanism of Action:
Gefitinib inhibits the epidermal growth factor receptor (EGFR) tyrosine kinase by binding to the adenosine triphosphate (ATP)-binding site of the enzyme. Thus the function of the EGFR tyrosine kinase in activating the Ras signal transduction cascade is inhibited; and malignant cells are inhibited. Gefitinib is the first selective inhibitor of the E...
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Absorption: Absorbed slowly after oral administration with mean bioavailability of 60%.
Protein binding: 90% primarily to serum albumin and alpha 1-acid glycoproteins.
Biotransformation: Primarily hepatic via CYP3A4. Three sites of biotransformation have been identified: metabolism of the N-propoxymorpholino-group, demethylation of the methoxy-substituent on the quinazoline, and oxidative defluorination of the halogenated phenyl group.
Route of elimination: Elimination is by metabolism (primarily CYP3A4) and excretion in feces. Excretion is predominantly via the feces (86%), with renal elimination of drug and metabolites accounting for less than 4% of the administered dose.
Half Life: 48 hours
Clearance: 595 mL/min
Toxicity: The acute toxicity of gefitinib up to 500 mg in clinical studies has been low. In non-clinical studies, a single dose of 12,000 mg/m2 (about 80 times the recommended clinical dose on a mg/m2 basis) was lethal to rats. Half this dose caused no mortality in mice. Symptoms of overdose include diarrhea and skin rash.
Affected organisms: Humans and other mammals
Food interaction:
Take without regard to meals.
Avoid fresh grapefruit and its juice during therapy as grapefruit may increase serum product levels.
Drug interaction:
TopotecanThe BCRP/ABCG2 inhibitor, Gefitnib, may increase the bioavailability and serum concentration of oral Topotecan. Monitor for change in the therapeutic and adverse effects of Topotecan if Gefitinib is initiated, discontinued or dose changed.
Dihydroquinidine barbiturateThe CYP3A4 inducer, dihydroquinidine barbiturate, may decrease the serum concentration and therapeutic effects of gefitinib.
HeptabarbitalThe CYP3A4 inducer, heptabarbital, may decrease the serum concentration and therapeutic effects of gefitinib.
CarbamazepineThe CYP3A4 inducer, carbamazepine, may decrease the serum concentration and therapeutic effects of gefitinib.
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of gefitinib by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of gefitinib if voriconazole is initiated, discontinued or dose changed.
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