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Plasma level studies with clomipramine (anafranil)

R B Jones, D K Luscombe

    The Journal of International Medical Research
    |January 1, 1977
    PubMed
    Summary
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    This study on clomipramine (Anafranil) for depression found that while clomipramine plasma levels varied, its metabolite desmethylclomipramine levels correlated with dosage. Steady-state concentrations were achieved by day 7.

    Area of Science:

    • Pharmacology
    • Clinical Pharmacy
    • Psychiatry

    Background:

    • Depressive illness is a common condition requiring effective pharmacotherapy.
    • Clomipramine (Anafranil) is a tricyclic antidepressant used in managing depression.
    • Understanding drug and metabolite pharmacokinetics is crucial for optimizing treatment.

    Purpose of the Study:

    • To investigate the pharmacokinetic profile of clomipramine and its metabolite, desmethylclomipramine, across different dosage regimens.
    • To assess the relationship between clomipramine dosage and plasma concentrations of the parent drug and its metabolite.
    • To determine the time to reach steady-state plasma levels in patients with depressive illness.

    Main Methods:

    • Patients with depressive illness received one of four clomipramine dosage regimens in a general practice setting.

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  • Plasma samples were collected at baseline and on days 7, 14, and 28 of treatment.
  • Plasma concentrations of clomipramine and desmethylclomipramine were analyzed.

    • Main Results:

    • Steady-state plasma concentrations for both clomipramine and desmethylclomipramine were achieved by day 7 of treatment.
    • No significant difference in mean steady-state plasma levels of clomipramine was observed across the four dosage groups.
    • Plasma concentrations of desmethylclomipramine showed a direct relationship with the administered clomipramine dose.
    • Significant intersubject variability (three to fourteen-fold) in clomipramine plasma levels was noted within each dosage group.

    Conclusions:

    • Clomipramine dosage does not appear to directly correlate with steady-state plasma levels of the parent drug.
    • The metabolite desmethylclomipramine exhibits a dose-dependent relationship in plasma concentrations.
    • Significant intersubject variability in clomipramine pharmacokinetics necessitates careful patient monitoring.
    • These findings have implications for optimizing clomipramine dosing strategies in depression management.