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Related Experiment Videos

Allopurinol kinetics.

K Hande, E Reed, B Chabner

    Clinical Pharmacology and Therapeutics
    |May 1, 1978
    PubMed
    Summary
    This summary is machine-generated.

    A new assay accurately measures allopurinol and oxipurinol in serum and urine. This study details allopurinol

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    Area of Science:

    • Pharmacokinetics
    • Analytical Chemistry
    • Biochemistry

    Background:

    • Allopurinol is a medication used to treat gout and hyperuricemia.
    • Understanding its metabolism and excretion is crucial for effective therapeutic use.
    • Previous methods for quantifying allopurinol and its metabolite, oxipurinol, had limitations.

    Purpose of the Study:

    • To develop and validate a sensitive spectrophotometric assay for allopurinol and oxipurinol.
    • To investigate the serum disappearance characteristics of allopurinol after intravenous and oral administration.
    • To determine the pharmacokinetic parameters of allopurinol and oxipurinol in humans.

    Main Methods:

    • Development of a spectrophotometric assay capable of detecting 5 X 10(-8) M allopurinol and oxipurinol in biological samples.

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  • Administration of allopurinol intravenously and orally to human subjects.
  • Measurement of serum concentrations of allopurinol and oxipurinol over time.
  • Estimation of renal clearance for both compounds.

    • Main Results:

    • The assay demonstrated high sensitivity for both analytes in serum and urine.
    • Serum concentrations of allopurinol and oxipurinol rapidly increased after administration, reaching >1 X 10(-5) M.
    • Mean serum oxipurinol concentration in patients on daily allopurinol was 3 X 10(-5) M.
    • Serum half-lives were approximately 39 minutes for allopurinol and 13.6 hours for oxipurinol.
    • Renal clearance estimates were provided for both drugs.
    • Metabolic conversion of allopurinol to oxipurinol was not significantly affected by long-term allopurinol therapy.

    Conclusions:

    • A reliable spectrophotometric method for quantifying allopurinol and oxipurinol has been established.
    • The study provides key pharmacokinetic data on allopurinol and oxipurinol absorption, distribution, and elimination in humans.
    • Findings suggest that the metabolic conversion of allopurinol to oxipurinol may involve a non-xanthine oxidase enzymatic pathway.