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Olanzapine Pathway, Pharmacokinetics

PA166165056 Last updated February 2019 Caroline F. Thorn.
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Drugs & chemicals
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Genes
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Conditions
23
Reactions
Olanzapine Pathway, Pharmacokinetics pathway diagram
Olanzapine Pathway, Pharmacokinetics — pathway diagram from PharmGKB / ClinPGx
Click to enlarge

About this pathway

Background

Olanzapine is an atypical, or second generation, antipsychotic is a first line choice for the treatment of schizophrenia [Articles:16805946, 21651311]. It has been shown to be more effective than aripiprazole, quetiapine, risperidone or ziprasidone based on PANSS scores (Positive and Negative Syndrome Scale) [Articles:28575321, 20238348]. Common side effects are weight gain and metabolic disturbances [Article:20238348].

Metabolism

The main circulating metabolites of olanzapine are desmethyl olanzapine and olanzapine-10- glucuronide [Article:26849777]. Conversion of olanzapine to desmethyl olanzapine is predominantly catalyzed by CYP1A2 with lesser roles for CYP2D6 and CYP2C8 [Articles:26856397, 26329789, 10511917]. The transcription of CYP1A2 can be increased by smoking, and as a result plasma concentration to dose ratio, C/D, of olanzapine by smokers is significantly lower (p<0.00001, n=1094) [Article:24595134] Inhibition of CYP1A2 by fluvoxamine also increases the C/D rario of olanzapine [Article:15545309]. Olanzapine can also be oxidized to olanzapine n-oxide by FMO3 or CYP2D6 and to 2’hydroxymethylolanzapine by CYP2D6 [Articles:16805946, 26856397, 10511917, 26329789]. While N-glucuronidation preferentially occurs at the 10 position it can also occur at the 4 position, however this is less common [Articles:26329789, 21750471]. Gender, BMI/fat mass and smoking all influence the metabolism of olanzapine [Article:10511917].

Reactions & interactions (23)

  • Biochemical Reaction
    olanzapine → olanzapine n-oxide
  • Biochemical Reaction
    olanzapine → unii-t148r8s95b
  • Biochemical Reaction
    olanzapine → n-demethyl olanzapine
  • Biochemical Reaction
    olanzapine → 2-hydroxymethyl olanzapine
  • Biochemical Reaction
    olanzapine → unii-a432w914yr
  • Catalysis
    FMO1 → Biochemical Reaction
  • Catalysis
    CYP3A4 → Biochemical Reaction
  • Catalysis
    FMO3 → Biochemical Reaction
  • Catalysis
    CYP2D6 → Biochemical Reaction
  • Catalysis
    CYP3A5 → Biochemical Reaction
  • Catalysis
    UGT1A4 → Biochemical Reaction
  • Catalysis
    UGT2B10 → Biochemical Reaction
  • Catalysis
    ABCB1 → Transport
  • Catalysis
    CYP3A4 → Biochemical Reaction
  • Catalysis
    CYP2C8 → Biochemical Reaction
  • Catalysis
    CYP1A2 → Biochemical Reaction
  • Catalysis
    CYP2D6 → Biochemical Reaction
  • Catalysis
    CYP3A43 → Biochemical Reaction
  • Catalysis
    CYP2D6 → Biochemical Reaction
  • Catalysis
    UGT1A4 → Biochemical Reaction
  • Catalysis
    UGT2B10 → Biochemical Reaction
  • Inhibition
    olanzapine → ABCB1
  • Transport
    olanzapine → olanzapine

Edit history (2)

  • 2017-06-13 Create
  • 2019-02-19 Update Updated to new illustrator formatting.
Olanzapine Pathway, Pharmacokinetics pathway diagram (enlarged)