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The change of p-aminohippuric acid disposition kinetics accompanied by growth in mice

J Hirate, I Horikoshi, J Watanabe

    Journal of Pharmacobio-Dynamics
    |November 1, 1985
    PubMed

    Insights

    Newborn mice show underdeveloped metabolism and delayed elimination of p-aminohippuric acid (PAH). This suggests immature renal tubular function and increased muscle permeability in infant mice, impacting PAH disposition kinetics.

    Area of Science:

    • Pharmacokinetics and Drug Metabolism
    • Developmental Physiology
    • Renal Function in Neonates

    Background:

    • P-aminohippuric acid (PAH) is a substrate used to assess renal tubular secretion.
    • Understanding developmental changes in drug disposition is crucial for neonatal care.
    • Immature metabolic and excretory pathways in neonates can alter drug pharmacokinetics.

    Purpose of the Study:

    • To investigate the disposition kinetics of p-aminohippuric acid (PAH) in mice of different age groups (1-day-old, 1-week-old, 3-week-old, and 8-week-old).
    • To determine the impact of age on PAH metabolism, renal excretion, and tissue distribution.
    • To elucidate the developmental maturation of renal tubular secretory function and its relation to PAH pharmacokinetics.

    Main Methods:

    • Intravenous administration of radiolabeled p-[glycyl-1-14C]aminohippuric acid to mice of varying ages.
    • Measurement of expiratory 14CO2 excretion over 24 hours to assess metabolic activity.
    • Analysis of blood radioactivity elimination curves to evaluate clearance and half-life.
    • Whole-body autoradiography to determine the tissue distribution of radioactivity, particularly in muscle.

    Main Results:

    • Expiratory 14CO2 excretion was negligible in 1-day-old and 1-week-old mice, indicating underdeveloped PAH metabolism.
    • Elimination of blood radioactivity was significantly delayed in 1-day-old and 1-week-old mice, suggesting immature renal tubular secretion.
    • Whole-body autoradiography revealed enhanced transfer of PAH from blood to muscle in younger mice, particularly 1-day-old, compared to older mice.
    • Increased muscular cell membrane permeability to PAH is proposed as the primary reason for enhanced muscle uptake in neonates.

    Conclusions:

    • Neonatal mice (1-day-old and 1-week-old) exhibit significantly different PAH disposition kinetics compared to older mice.
    • The underdeveloped metabolic capacity and delayed renal excretion in infant mice point to immature physiological functions.
    • Enhanced muscle tissue uptake in neonates is likely due to increased cell membrane permeability, affecting overall PAH distribution.

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