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Procainamide disposition in obesity.

P B Christoff, D R Conti, C Naylor

    Drug Intelligence & Clinical Pharmacy
    |July 1, 1983
    PubMed
    Summary
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    Obese individuals exhibit altered procainamide (PA) pharmacokinetics, with increased renal clearance of PA but decreased renal clearance of its metabolite NAPA. This suggests patient physiology impacts drug disposition.

    Area of Science:

    • Pharmacology
    • Clinical Pharmacy
    • Drug Metabolism

    Background:

    • Understanding drug pharmacokinetics in obesity is crucial for safe and effective dosing.
    • Procainamide (PA) is an antiarrhythmic drug whose disposition may be affected by body composition.
    • Obesity can alter drug distribution, metabolism, and excretion, necessitating pharmacokinetic studies.

    Purpose of the Study:

    • To investigate the pharmacokinetics of intravenous procainamide (PA) in obese versus normal-weight subjects.
    • To determine how pharmacokinetic parameters relate to ideal body weight (IBW) and total body weight (TBW).
    • To elucidate the impact of obesity on PA and its active metabolite, N-acetylprocainamide (NAPA), disposition.

    Main Methods:

    • Studied intravenous procainamide (PA) pharmacokinetics in seven obese and seven normal subjects.

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  • Measured serum concentrations and urinary excretion rates of PA and NAPA using high-performance liquid chromatography.
  • Related pharmacokinetic parameters to ideal body weight (IBW) and total body weight (TBW).

    • Main Results:

    • Volume of distribution at steady state (Vssd) was similar per unit IBW for both groups.
    • Plasma clearance of PA, corrected for body surface area, was higher in obese subjects per IBW.
    • Obese subjects showed similar metabolic clearances but significantly increased renal clearance of PA per body surface area, likely due to enhanced tubular secretion; however, they had lower renal clearances of NAPA.

    Conclusions:

    • Obesity significantly alters procainamide (PA) renal clearance, increasing tubular secretion of PA while decreasing renal clearance of its metabolite NAPA.
    • Variability in PA disposition is influenced by patient physiology (obesity) and the method used for parameter normalization (IBW vs. TBW).
    • These findings highlight the importance of considering body weight and normalization methods in procainamide dosing for obese patients.