gefitinib

Ligand id: 4941

Name: gefitinib

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Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 8
Topological polar surface area 68.74
Molecular weight 446.15
XLogP 3.06
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

No information available.
Summary of Clinical Use
Used in the treatment of various cancers including those of the breast and lung. In July 2015, the US FDA approved gefitinib as a first-line treatment for metastatic non-small cell lung cancer (NSCLC).
Mechanism Of Action and Pharmacodynamic Effects
Gefitinib inhibits intracellular phosphorylation of numerous tyrosine kinases associated with transmembrane cell surface receptors, including epidermal growth factor receptor (EGFR), tyrosine kinase activation of which may initiate intracellular signaling events leading to cell proliferation and influencing processes critical to cell survival and tumor progression (e.g., angiogenesis, apoptosis, metastasis). Further studies are required to elucidate the precise mechanism of antineoplastic activity and to determine if any correlation exists between EGFR receptor expression and gefitinib response.
Pharmacokinetics
Absorption/Distribution
It takes 3-7h for an oral dose of gefitinib to reach peak plasma concentration, with a bioavailability of 60% (90% bound to serum albumin and α1-acid glycoproteins). Gefitinib is known to cross the placenta. Rat data indicate that this drug and its metabolites are found in milk. It is not known whether this distribution also occurrs in human milk.
Biotransformation/Metabolism
CYP3A4 in the liver is the primary matabolizing enzyme.
Elimination
Gefitinib is eliminated mainly as metabolites via feces (86%) and urine (<4%).
Population pharmacokinetics
No clinically significant change in pharmacokinetics due to age, weight, ethnicity or gender has been reported, but safety and efficacy has not been established in children <18yrs old.
Organ function impairment
Not unexpectedly, since gefitinib is cleared principally by the liver, patients with hepatic impairment exhibit increased systemic exposure to the drug. However, in patients with moderate to severe elevations of hepatic enzymes and liver metastases, pharmacokinetic profile is similar to that in patients without hepatic abnormalities. The effect of severe renal impairment on pharmacokinetics has not been not determined, so advice is to use with caution
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