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Related Experiment Videos

Plasma binding variations of amitriptyline and nortriptyline

E Pike, B Skuterud

    Clinical Pharmacology and Therapeutics
    |August 1, 1982
    PubMed
    Summary

    Plasma protein binding of amitriptyline (AT) and nortriptyline (NT) varies significantly. This variation is crucial for understanding the inconsistent link between total drug levels and antidepressant effects.

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    Area of Science:

    • Pharmacology
    • Clinical Chemistry

    Background:

    • The correlation between total plasma concentration and the therapeutic effect of amitriptyline (AT) and nortriptyline (NT) is often uncertain.
    • Plasma protein binding significantly influences drug distribution and efficacy.

    Purpose of the Study:

    • To investigate the impact of plasma protein binding variability on the relationship between total and unbound concentrations of AT and NT.
    • To understand how this variability affects the antidepressive effects of AT and NT.

    Main Methods:

    • Analysis of plasma binding for AT and NT in 131 patient plasma samples using equilibrium dialysis at 37°C for 3 hours.
    • Quantification of unbound drug fractions and total drug concentrations.
    • Assessment of correlations between unbound and total drug levels, and with plasma components like triglycerides, cholesterol, and orosomucoid.

    Main Results:

    • A twofold variation was observed in the percentage of unbound AT (3.5%–8.6%) and NT (5.4%–11.3%).
    • No correlation was found between the percentage of unbound drug and total drug concentration for either AT or NT.
    • At therapeutic concentrations, AT was bound to orosomucoid (alpha 1-acid glycoprotein) and albumin (66.6% and 63.5%, respectively).

    Conclusions:

    • Variations in plasma protein binding are a key factor contributing to the uncertain correlation between total plasma concentrations and the clinical effects of AT and NT.
    • Unbound drug concentration, rather than total concentration, is a more relevant measure for assessing therapeutic efficacy and potential toxicity.

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