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Disopyramide concentrations in saliva

M L Aitio, R Virtanen, R Lammintausta

    International Journal of Clinical Pharmacology, Therapy, and Toxicology
    |February 1, 1982
    PubMed
    Summary
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    Saliva concentrations of disopyramide are unreliable for predicting plasma levels. This study found wide interindividual variations in disopyramide and metabolite levels, impacting drug monitoring accuracy.

    Area of Science:

    • Pharmacokinetics
    • Drug Metabolism
    • Clinical Pharmacology

    Background:

    • Disopyramide is an antiarrhythmic drug with variable absorption and metabolism.
    • Understanding drug concentrations in different bodily fluids is crucial for therapeutic drug monitoring.
    • Saliva offers a non-invasive alternative for drug level assessment, but its reliability needs validation.

    Purpose of the Study:

    • To investigate the relationship between saliva and plasma concentrations of disopyramide and its metabolite, mono-N-dealkyldisopyramide.
    • To assess the protein binding of disopyramide and its impact on salivary concentrations.
    • To determine the reliability of salivary disopyramide levels for predicting plasma concentrations.

    Main Methods:

    • Ten healthy volunteers received a single oral dose of 400 mg disopyramide.

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  • Saliva and plasma samples were collected at various time points.
  • Concentrations of disopyramide, its metabolite, and plasma protein binding were measured.
  • Salivary flow rate and pH were also recorded.

    • Main Results:

    • Disopyramide exhibited a concentration-dependent inhibition of salivary flow rate.
    • Good correlations were observed between salivary and plasma concentrations of disopyramide and its metabolite.
    • The unbound fraction of disopyramide in plasma varied significantly between individuals.
    • Saliva-to-plasma (S/P) ratios were highest at peak drug concentrations.
    • No significant correlation was found between S/P ratio and salivary pH.

    Conclusions:

    • Salivary disopyramide concentrations are not reliable predictors of total or free plasma concentrations.
    • Significant interindividual variability exists in disopyramide pharmacokinetics.
    • Non-invasive monitoring of disopyramide via saliva may be limited due to poor predictive value.