Abstract
Gefitinib (Iressa, AstraZeneca) has been widely used for the treatment of locally advanced or metastatic non-small cell lung cancer. A number of studies have been reported on its pharmacokinetics profiles, especially on the metabolism. In this review, we have comprehensively summarized the pharmacokinetic characteristics of gefitinib: absorption, distribution, metabolism and excretion (ADME). Overall, gefitinib reached the maximum plasma level relatively fast and distributed extensively. It underwent extensive biotransformation and predominantly excreted in feces, with less than 7% in the urine. CYP450 enzymes played critical roles in the process of gefitinib metabolism. The major enzyme involved in the metabolism was CYP3A4, with other CYP450 enzymes playing a secondary role. A high clearance of gefitinib might result in drug resistance by lowering drug concentration. The enhanced efflux and decreased uptake by transporters were important resistance mechanisms. The transporters involved in pharmacokinetics of gefitinib consist of the ATP-binding cassette and the solute carrier superfamily. Understanding the pharmacokinetics property of gefitinib may provide valuable and new information for dealing with drug resistance and making personalized therapy regarding their interindividual variability.
Keywords: Enzymes, gefitinib, metabolism, pharmacokinetics, transporters.
Current Drug Delivery
Title:Pharmacokinetics of Gefitinib: Roles of Drug Metabolizing Enzymes and Transporters
Volume: 14 Issue: 2
Author(s): Can Zhao, Shu-Yan Han and Ping-Ping Li
Affiliation:
Keywords: Enzymes, gefitinib, metabolism, pharmacokinetics, transporters.
Abstract: Gefitinib (Iressa, AstraZeneca) has been widely used for the treatment of locally advanced or metastatic non-small cell lung cancer. A number of studies have been reported on its pharmacokinetics profiles, especially on the metabolism. In this review, we have comprehensively summarized the pharmacokinetic characteristics of gefitinib: absorption, distribution, metabolism and excretion (ADME). Overall, gefitinib reached the maximum plasma level relatively fast and distributed extensively. It underwent extensive biotransformation and predominantly excreted in feces, with less than 7% in the urine. CYP450 enzymes played critical roles in the process of gefitinib metabolism. The major enzyme involved in the metabolism was CYP3A4, with other CYP450 enzymes playing a secondary role. A high clearance of gefitinib might result in drug resistance by lowering drug concentration. The enhanced efflux and decreased uptake by transporters were important resistance mechanisms. The transporters involved in pharmacokinetics of gefitinib consist of the ATP-binding cassette and the solute carrier superfamily. Understanding the pharmacokinetics property of gefitinib may provide valuable and new information for dealing with drug resistance and making personalized therapy regarding their interindividual variability.
Export Options
About this article
Cite this article as:
Zhao Can, Han Shu-Yan and Li Ping-Ping, Pharmacokinetics of Gefitinib: Roles of Drug Metabolizing Enzymes and Transporters, Current Drug Delivery 2017; 14 (2) . https://dx.doi.org/10.2174/1567201813666160709021605
DOI https://dx.doi.org/10.2174/1567201813666160709021605 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
Call for Papers in Thematic Issues
Advancements in Robotic and AI-based Drug Discovery and Delivery for Neurological Disorders
Neurological disorders, including Alzheimer's disease, Parkinson's disease, epilepsy, and brain tumors, pose significant challenges in drug delivery due to the blood-brain barrier's intricate structure and the complexity of neuronal networks. Traditional drug delivery methods often fall short in reaching therapeutic concentrations within the central nervous system, limiting treatment efficacy and ...read more
Advances of natural products, bio-actives and novel drug delivery system against emerging viral infections
Due to the increasing prevalence of viral infections and the ability of these human pathogens to develop resistance to current treatment strategies, there is a great need to find and develop new compounds to combat them. These molecules must have low toxicity, specific activity and high bioavailability. The most suitable ...read more
Electrospun Fibers as Drug Delivery Systems
In recent years, electrospun fibers have attracted considerable attention as potential platforms for drug delivery due to their distinctive properties and adaptability. These fibers feature a notable surface area-to-volume ratio and can be intentionally designed with high porosity, facilitating an increased capacity for drug loading and rendering them suitable for ...read more
Emerging Nanotherapeutics for Mitigation of Neurodegenerative Disorders
Conditions affecting the central nervous system (CNS) present a significant hurdle due to limited access of both treatments and diagnostic tools for the brain. The blood-brain barrier (BBB) acts as a barrier, restricting the passage of molecules from the bloodstream into the brain. The most formidable challenge facing scientists is ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Oncogenic Fusion Tyrosine Kinases as Molecular Targets for Anti-Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Targeting Chemokine Receptor CXCR4 for Treatment of HIV-1 Infection, Tumor Progression, and Metastasis
Current Topics in Medicinal Chemistry Future Oncotargets: Targeting Overexpressed Conserved Protein Targets in Androgen Independent Prostate Cancer Cell Lines
Anti-Cancer Agents in Medicinal Chemistry From the Deepest Sea Shelf to the Uppermost Kitchen Cabinet Shelf: The Quest for Novel TNF-α Inhibitors
Current Topics in Medicinal Chemistry Non-Small Cell Lung Cancer: From Cytotoxic Systemic Chemotherapy to Molecularly Targeted Therapy
Current Medicinal Chemistry - Anti-Cancer Agents Current Status and Future Perspective for Research on Medicinal Plants with Anticancerous Activity and Minimum Cytotoxic Value
Current Drug Targets Inhibitors of the Hedgehog Signal Transduction Pathway
Current Cancer Therapy Reviews The Redox Regulation of Thiol Dependent Signaling Pathways in Cancer
Current Pharmaceutical Design Patent Selections
Recent Patents on Biomarkers Autoimmune Channelopathies of the Nervous System
Current Neuropharmacology Clinical Applications of Mesenchymal Stem Cells in Laryngotracheal Reconstruction
Current Stem Cell Research & Therapy Advances in the Development of Anticancer HSP-based Vaccines
Current Medicinal Chemistry Understanding the Molecular Properties and Metabolism of Top Prescribed Drugs
Current Topics in Medicinal Chemistry Meet Our Editorial Board Member
Pharmaceutical Nanotechnology Anti-Infective Quinone Derivatives of Recent Patents
Recent Patents on Anti-Infective Drug Discovery Tumor Stem Cell Niches: A New Functional Framework for the Action of Anticancer Drugs
Recent Patents on Anti-Cancer Drug Discovery Molecular Dynamics and Structural Studies of the Ets Domain-DNA Complexes
Current Bioinformatics The Use of Ghrelin and Ghrelin Receptor Agonists as a Treatment for Animal Models of Disease: Efficacy and Mechanism
Current Pharmaceutical Design The Role of Histone Demethylase GASC1 in Cancer and its Therapeutic Potential
Current Cancer Therapy Reviews CDK Inhibitors: From the Bench to Clinical Trials
Current Drug Targets