Chapter Five - Gefitinib

Abstract

Gefitinib (Iressa®) is a selective inhibitor of epidermal growth factor, a growth factor that plays a pivotal role in the control of cell growth, apoptosis, and angiogenesis. Gefitinib is clinically used for the treatment of chemoresistant non-small cell lung cancer patients. Gefitinib is freely soluble in dimethylsulphoxide but slightly soluble in methanol and ethanol. Several methods of gefitinib synthesis are included in this review. UV spectroscopy of gefitinib showed a λmax of approximately 331nm, whereas IR spectroscopy principal peaks were observed at 3400cm(-1) (NH), 2956cm(-1) (CH2, CH, alkyl), 1625cm(-1) (CC, CN), 1500cm(-1) (HCCH, aryl), 1110cm(-1) (CO), 1028cm(-1) (CF). In addition, different analytical methods for determination of gefitinib are also described in this review. Pharmacokinetically, after oral administration, gefitinib is slowly absorbed with bioavailability of approximately 60% in human. Gefitinib is metabolized extensively in the liver into five metabolites by cytochrome P450s, primarily by CYP3A4 and to a lesser extent by CYP3A5 and CYP2D6. Gefitinib is eliminated mainly hepatically with total plasma clearance of 595mL/min after intravenous administration. Most of the adverse effects associated with gefitinib therapy are mild to moderate in severity and are usually reversible and manageable with appropriate intervention, such as diarrhea, dry skin, rash, nausea, and vomiting.