Metabolite Characterization of Anti-cancer Agent Gefitinib in Human Hepatocytes

ISSN: 1874-0758 (Online)
ISSN: 1872-3128 (Print)


Volume 8, 2 Issues, 2014


Download PDF Flyer




Drug Metabolism Letters

Aims & ScopeAbstracted/Indexed in


Submit Abstracts Online Submit Manuscripts Online

Editor-in-Chief:
Chandra Prakash
Department of Drug Metabolism and Pharmacokinetics
Biogen Idec
Cambridge, MA
USA


View Full Editorial Board

Subscribe Purchase Articles Order Reprints


Metabolite Characterization of Anti-cancer Agent Gefitinib in Human Hepatocytes

Author(s): Prashant Surve, Selvan Ravindran, Arghya Acharjee, Himanshu Rastogi, Sudipta Basu and Pradnya Honrao

Affiliation: Departments of Bio- Analytical and Biotransformation, Drug Metabolism and Pharmacokinetics Unit, Sai Life Sciences Limited, Building 1, Plot No 2, Chrysalis Enclave, International Biotech Park, Pune 411057, Maharashtra, India.

Abstract

Intensive Biotransformation studies on Gefitinib could play a significant role in designing and synthesizing new drugs around the core structure of Gefitinib. These studies may be useful in developing an entirely new drug by blocking the metabolic spots in Gefitinib. Gefitinib (Iressa) was the first oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Gefitinib shows toxicity to cancer cells and has the capability to inhibit the growth of cancer cells. Gefitinib is considered as one of the selective EGFR inhibitors to be available in clinical practice. In 2003, FDA had approved Gefitinib for metastatic non-small-cell lung cancer therapy (NSCLC). However, it was observed that NSCLC Patients who responded to treatment developed resistance to Gefitinib. Hence, in the present study Gefitinib was incubated with hepatocytes to identify both phase-I and Phase-II metabolites. Identified Phase –I metabolites were due to oxidative defluorination, N-dealkylation and loss of morpholine ring. One of the phase-II metabolites identified i.e. the glutathione adduct suggests the need to modify the structure of the drug for higher potency and safety.

Keywords: Drug metabolism, gefitinib, liquid chromatography, mass spectrometry, metabolites.

Purchase Online Order Reprints Order Eprints Rights and Permissions

  
  



Article Details

Volume: 7
Issue Number: 2
First Page: 126
Last Page: 136
Page Count: 11
DOI: 10.2174/1872312808666140317154110
Advertisement

Related Journals




Webmaster Contact: urooj@benthamscience.org Copyright © 2014 Bentham Science