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Naproxen Pathway, Pharmacokinetics

PA166163741 Last updated January 2019 Caroline F. Thorn.
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Drugs & chemicals
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Genes
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Conditions
16
Reactions
Naproxen Pathway, Pharmacokinetics pathway diagram
Naproxen Pathway, Pharmacokinetics — pathway diagram from PharmGKB / ClinPGx
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About this pathway

Background

Naproxen is an NSAID non-steroidal anti-inflammatory drug used in the treatment of arthritis and pain [Article:24175972]. It acts mainly by inhibition of the COX 1 and COX2 enzymes coded for by PTGS1 and PTGS2 respectively [Article:11496855]. Side effects include risk for gastrointestinal bleeding and cardiovascular events, although recent studies comparing NSAIDs for cardiovascular risk suggested that naproxen is one of the lowest risk options [Articles:24175972, 21980265].

Metabolism

Experiments with microsomes and expressed proteins indicate that the main demethylation pathway for both stereoisomers of naproxen is catalyzed by CYP2C9 and CYP1A2 [Article:8866821]. The parent drug can be glucuronidated, mainly by UGT2B7, and the desmethyl metabolite can be glucuronidated to form either the phenolic glucuronide or the acyl glucuronide [Article:16187975].

Reactions & interactions (16)

  • Biochemical Reaction
    naproxen naproxen glucuronide
  • Biochemical Reaction
    naproxen desmethylnaproxen
  • Biochemical Reaction
    desmethylnaproxen 6-o-desmethylnaproxen iso acyl glucuronide
  • Biochemical Reaction
    desmethylnaproxen 6-o-desmethylnaproxen 6-glucuronide
  • Catalysis
    UGT1A9 Biochemical Reaction
  • Catalysis
    UGT2B7 Biochemical Reaction
  • Catalysis
    UGT1A6 Biochemical Reaction
  • Catalysis
    CYP2C9 Biochemical Reaction
  • Catalysis
    CYP1A2 Biochemical Reaction
  • Catalysis
    UGT1A6 Biochemical Reaction
  • Catalysis
    UGT1A3 Biochemical Reaction
  • Catalysis
    UGT1A1 Biochemical Reaction
  • Catalysis
    UGT1A9 Biochemical Reaction
  • Catalysis
    UGT2B7 Biochemical Reaction
  • Catalysis
    UGT1A1 Biochemical Reaction
  • Catalysis
    UGT1A9 Biochemical Reaction

Edit history (2)

  • 2017-05-03 Create
  • 2019-01-31 Update Updated to new illustrator formatting
Naproxen Pathway, Pharmacokinetics pathway diagram (enlarged)