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Related Experiment Videos

Intraindividual variation in drug disposition.

A P Alvares, A Kappas, J L Eiseman

    Clinical Pharmacology and Therapeutics
    |October 1, 1979
    PubMed
    Summary

    Drug metabolism varies between individuals due to genetics and environment. Intraindividual variations are low for some drugs like antipyrine but high for others like phenacetin, indicating environmental influences on drug metabolism rates.

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    Area of Science:

    • Pharmacology
    • Drug Metabolism
    • Biochemistry

    Background:

    • Interindividual differences in drug metabolism are significant, influenced by genetic and environmental factors.
    • Understanding intraindividual variability is crucial for accurate drug response prediction.
    • Previous studies highlighted variability but lacked detailed analysis of specific drug metabolic pathways.

    Purpose of the Study:

    • To investigate the extent of intraindividual variability in drug metabolism rates.
    • To compare variability for drugs with different metabolic pathways and extraction ratios.
    • To assess the reliability of antipyrine as a marker for drug metabolism studies.

    Main Methods:

    • Subjects received specific drugs (antipyrine, phenylbutazone, phenacetin) on multiple occasions.

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  • Plasma drug concentrations and half-lives were measured over time.
  • Assay procedures were validated to exclude technical variability.

    • Main Results:

    • Antipyrine and phenylbutazone showed low intraindividual metabolic variability.
    • Phenacetin exhibited significantly higher intraindividual variability in plasma half-life and AUC.
    • Variations in metabolism were not attributed to assay errors.

    Conclusions:

    • Intraindividual variability in drug metabolism is drug-dependent, correlating with metabolic pathways and hepatic extraction.
    • Antipyrine is a reliable drug for studying drug metabolism in humans.
    • The antipyrine test may identify individuals with environmental factors affecting drug metabolism.