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Pipemidic acid: absorption, distribution, and excretion.

M Shimizu, S Nakamura, Y Takase

    Antimicrobial Agents and Chemotherapy
    |April 1, 1975
    PubMed
    Summary
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    Pipemidic acid demonstrates good oral absorption and wide tissue distribution in multiple species. The drug is primarily excreted unchanged in urine and feces, with a very low lethal dose, indicating good safety.

    Area of Science:

    • Pharmacology
    • Drug Metabolism
    • Toxicology

    Background:

    • Pipemidic acid is an antibacterial agent.
    • Understanding its pharmacokinetic and toxicological profile is crucial for clinical use.

    Purpose of the Study:

    • To investigate the absorption, distribution, metabolism, excretion, and toxicity of pipemidic acid.
    • To determine the active form of the drug in vivo.

    Main Methods:

    • Oral administration of pipemidic acid to mice, rats, dogs, and monkeys.
    • Measurement of plasma and tissue concentrations.
    • Analysis of urinary and fecal excretion.
    • Determination of protein binding.
    • Acute and subchronic toxicity studies.

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    Main Results:

    • Good oral absorption with peak plasma levels of 4-12 µg/ml.
    • Significant distribution to organs and tissues, with higher concentrations in bile and urine.
    • 25-88% of the dose excreted unchanged in urine; remainder in feces (in humans).
    • Low protein binding (20-30%).
    • High mean lethal dose (>16,000 mg/kg in mice) and no observed abnormalities in subchronic toxicity studies.

    Conclusions:

    • Pipemidic acid is well-absorbed orally and distributed widely.
    • The unchanged drug is the active form, excreted primarily in urine.
    • Pipemidic acid exhibits a favorable safety profile with low acute and subchronic toxicity.