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Hepatic enzyme induction patterns and phenothiazine side effects.

J H Wright, S B Whitaker, C B Welch

    Clinical Pharmacology and Therapeutics
    |October 1, 1983
    PubMed
    Summary
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    Phenothiazine treatment in psychotic patients can induce D-glucaric acid excretion, potentially reducing neurological side effects. This suggests individual metabolic differences influence drug response and side effect severity.

    Area of Science:

    • Pharmacology
    • Neuroscience
    • Biochemistry

    Background:

    • Phenothiazines are antipsychotic drugs used to treat psychosis.
    • Neurological side effects are common with phenothiazine treatment.
    • Individual variability in drug response and side effects is a significant clinical challenge.

    Purpose of the Study:

    • To investigate the relationship between D-glucaric acid excretion and phenothiazine treatment in psychotic patients.
    • To determine if changes in D-glucaric acid excretion correlate with the incidence and severity of neurological side effects.
    • To explore the role of enzyme induction in phenothiazine metabolism and its clinical implications.

    Main Methods:

    • Measurement of urinary D-glucaric acid excretion in psychotic patients undergoing phenothiazine treatment for 12 days.

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  • Comparison of D-glucaric acid levels between patients and a control group without psychiatric illness.
  • Assessment of neurological side effects in relation to D-glucaric acid excretion levels.

    • Main Results:

    • Approximately 50% of psychotic patients exhibited a rise in D-glucaric acid excretion during phenothiazine treatment, indicative of enzyme induction.
    • Patients with increased D-glucaric acid excretion reported fewer and less severe neurological side effects.
    • A significant correlation was observed between higher D-glucaric acid levels and reduced neurological adverse events.

    Conclusions:

    • Individual differences in phenothiazine metabolism, suggested by varying D-glucaric acid excretion, may explain differential clinical responses.
    • Enzyme induction, as indicated by D-glucaric acid levels, appears to be a protective factor against phenothiazine-induced neurological side effects.
    • Monitoring D-glucaric acid excretion could offer insights into predicting and managing phenothiazine treatment outcomes.