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Sparteine oxidation polymorphism in Denmark.

K Brøsen, S V Otton, L F Gram

    Acta Pharmacologica Et Toxicologica
    |November 1, 1985
    PubMed
    Summary
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    Sparteine oxidation exhibits genetic variability in humans, with a small percentage identified as poor metabolizers (PM) and the majority as extensive metabolizers (EM). This confirms sparteine as a valuable tool for pharmacogenetic research.

    Area of Science:

    • Pharmacogenetics
    • Drug Metabolism
    • Human Genetics

    Background:

    • Sparteine is an alkaloid with known polymorphic oxidation in humans.
    • Understanding sparteine metabolism is crucial for its use as a probe drug.

    Purpose of the Study:

    • To investigate the polymorphic oxidation of sparteine in a Danish population.
    • To characterize poor metabolizers (PM) and extensive metabolizers (EM) of sparteine.
    • To evaluate sparteine as a probe drug in pharmacogenetic studies.

    Main Methods:

    • Phenotyping 301 healthy Danish volunteers based on sparteine oxidation.
    • Analyzing urinary sparteine and dehydrosparteine metabolites over 12 hours.
    • Calculating the metabolic ratio (MR) to differentiate metabolizer phenotypes.

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    Main Results:

    • 7.3% of subjects were identified as poor metabolizers (PM), while 92.7% were extensive metabolizers (EM).
    • Metabolic ratios (MR) in urine clearly distinguished between PM (30-394) and EM (0.11-12.6).
    • Urinary excretion of 2- and 5-dehydrosparteine also effectively discriminated between PM and EM phenotypes.
    • Age, sex, and smoking habits did not significantly affect the metabolic ratio.

    Conclusions:

    • Sparteine oxidation is a polymorphic trait in the studied Danish population.
    • The metabolic ratio and urinary metabolite excretion effectively identify sparteine metabolizer phenotypes.
    • Sparteine is confirmed as a reliable probe drug for pharmacogenetic investigations.