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Polymorphic acetylation procainamide in man.

M M Reidenberg, D E Drayer, M Levy

    Clinical Pharmacology and Therapeutics
    |June 1, 1975
    PubMed
    Summary
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    N-Acetylprocainamide (NAPA) and procainamide are metabolized differently based on acetylator phenotype. Rapid acetylators show higher plasma NAPA/procainamide ratios, indicating procainamide is acetylated by polymorphic N-acetyltransferase.

    Area of Science:

    • Pharmacology
    • Clinical Chemistry
    • Genetics

    Background:

    • Procainamide is an antiarrhythmic drug.
    • N-Acetylprocainamide (NAPA) is a known metabolite of procainamide.
    • Individual differences in drug metabolism can affect therapeutic outcomes.

    Purpose of the Study:

    • To investigate the relationship between acetylator phenotype and the plasma and urine concentrations of NAPA and procainamide.
    • To determine if procainamide is acetylated by the polymorphic N-acetyltransferase enzyme in humans.

    Main Methods:

    • Dapsone phenotyping was used to determine acetylator phenotype (slow vs. rapid).
    • Plasma and urine concentrations of NAPA and procainamide were measured using thin-layer chromatography (TLC) densitometry.
    • Renal clearance of both drugs and urine pH were assessed.

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    Main Results:

    • Plasma NAPA/procainamide ratios were significantly higher in rapid acetylators compared to slow acetylators.
    • Renal clearance of NAPA and procainamide did not differ between acetylator phenotypes.
    • Urine NAPA/procainamide ratios were also higher in rapid acetylators.

    Conclusions:

    • Procainamide acetylation is likely mediated by the polymorphic N-acetyltransferase in humans.
    • Acetylator phenotype significantly influences the NAPA/procainamide ratio.
    • NAPA likely contributes to the antiarrhythmic activity of procainamide, particularly in rapid acetylators.