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Gefitinib Pathway, Pharmacokinetics

PA152325160 Last updated June 2019 Tina Hernandez-Boussard, David Flockhart, Xing Jian Lou.
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Drugs & chemicals
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Conditions
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Reactions
Gefitinib Pathway, Pharmacokinetics pathway diagram
Gefitinib Pathway, Pharmacokinetics — pathway diagram from PharmGKB / ClinPGx
Click to enlarge

About this pathway

Gefitinib is an anilinoquinazoline compound with the chemical name 4-quinazolinamine, N-(3-chloro-4-flurophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]. Gefitinib inhibits receptor tyrosine kinases (TKs) including the epidermal growth factor recpetor (EGRF)-TK. Gefitinib also inhibits ATP-binding cassette transporter-mediated drug efflux, which in turn strongly increases the intracellular concentrations of co-administrated drug molecules that are transporter substrates.

After oral administration, gefitinib is widely distributed throughout the body. Gefitinib is metabolized in the liver by cytochrome P450s, primarily by CYP3A4, but CYP3A5 and CYP2D6 also play minor roles in gefitinib metabolism. In addition to its role as an ABC transporter inhibitor, gefitinib has also been implicated as an inhibitor of CYP2C19 and CYP2D6 activity. Therefore, gefitinib may inhibit the metabolism of co-administered drugs that are substrates of CYP2C19 and CYP2D6 and weakly inhibits the metabolism of substrates of CYP2C9, CYP3A4, and CYP1A2.

Reactions & interactions (29)

  • Biochemical Reaction
    gefitinib → gefitinib M537194
  • Biochemical Reaction
    gefitinib → gefitinib M523595
  • Biochemical Reaction
    gefitinib → gefitinib M387783
  • Catalysis
    CYP3A4 → Biochemical Reaction
  • Catalysis
    CYP1A1 → Biochemical Reaction
  • Catalysis
    CYP3A5 → Biochemical Reaction
  • Catalysis
    ABCC10 → Transport
  • Catalysis
    CYP3A4 → Biochemical Reaction
  • Catalysis
    CYP2D6 → Biochemical Reaction
  • Catalysis
    CYP3A5 → Biochemical Reaction
  • Catalysis
    CYP3A4 → Biochemical Reaction
  • Catalysis
    CYP1A1 → Biochemical Reaction
  • Catalysis
    ABCB1 → Transport
  • Catalysis
    ABCG2 → Transport
  • Inhibition
    gefitinib → UGT1A7
  • Inhibition
    gefitinib → UGT2B7
  • Inhibition
    gefitinib → UGT1A1
  • Inhibition
    gefitinib → UGT1A9
  • Inhibition
    gefitinib → ABCB1
  • Inhibition
    gefitinib → EGFR
  • Inhibition
    gefitinib → CYP2D6
  • Inhibition
    gefitinib → ABCG2
  • Leads To
    gefitinib → Diarrhea
  • Leads To
    gefitinib → Exanthema
  • Leads To
    gefitinib → Exanthema
  • Leads To
    gefitinib → Diarrhea
  • Leads To
    EGFR → EGFR Inhibitors Pathway (PD)
  • Transport
    gefitinib → gefitinib
  • Transport
    gefitinib → gefitinib

Edit history (4)

  • 2006-05-06 Create
  • 2012-03-04 Update
  • 2019-06-18 Update Updated illustrator and image map to new format and included additions of candidate genes based on PMIDs added.
  • 2019-06-24 Update Update to new gpml format.
Gefitinib Pathway, Pharmacokinetics pathway diagram (enlarged)