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Nonlinear desipramine pharmacokinetics: a case study.

J E Dugas, D S Bishop

    Journal of Clinical Psychopharmacology
    |February 1, 1985
    PubMed
    Summary
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    This study describes nonlinear desipramine pharmacokinetics where drug levels changed disproportionately with dose. This suggests saturated liver metabolism, requiring careful dose adjustments and monitoring of desipramine serum concentrations.

    Area of Science:

    • Pharmacology
    • Clinical Pharmacy
    • Drug Metabolism

    Background:

    • Desipramine is a tricyclic antidepressant used to treat depression.
    • Therapeutic drug monitoring of desipramine serum concentrations is common practice.
    • Standard pharmacokinetic models assume linear dose-concentration relationships.

    Observation:

    • A patient exhibited disproportionate changes in serum desipramine concentrations relative to dose adjustments.
    • Serum concentrations did not decrease linearly as the dose was reduced from 400 mg/day to 50 mg/day.
    • Steady-state concentrations followed a nonlinear pattern.

    Findings:

    • The patient's desipramine pharmacokinetics were nonlinear, indicating saturation of metabolic pathways.
    • A curvilinear relationship between serum drug concentration and dose was observed.

    Related Experiment Videos

  • Hepatic metabolism of desipramine likely became saturated at higher doses.

    • Implications:

    • Clinicians must exercise caution when predicting desipramine doses based on serum concentrations.
    • Titrating desipramine doses requires careful consideration of potential nonlinear behavior.
    • This case highlights the importance of recognizing nonlinear pharmacokinetics in individual patients for safe and effective treatment.