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Clofibrate and enzymatic induction in man.

G Houin, J P Tillement

    International Journal of Clinical Pharmacology and Biopharmacy
    |April 1, 1978
    PubMed
    Summary

    Clofibrate did not alter antipyrine metabolism or glucaric acid excretion in humans at tested doses. However, rifampicin reduced clofibrate metabolite levels, suggesting clofibrate metabolism is inducible and may require dose adjustment when co-administered.

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    Area of Science:

    • Pharmacology
    • Drug Metabolism
    • Human Physiology

    Background:

    • Clofibrate is known to induce hepatic microsomal enzymes in rats.
    • The effect of clofibrate on human drug metabolism and excretion pathways is not fully elucidated.
    • Understanding drug-drug interactions involving clofibrate is crucial for safe and effective therapeutic use.

    Purpose of the Study:

    • To investigate the effect of oral clofibrate on antipyrine half-life and urinary glucaric acid excretion in human volunteers.
    • To explore the influence of rifampicin, a known enzyme inducer, on clofibrate metabolism in humans.
    • To assess potential interactions between clofibrate and rifampicin.

    Main Methods:

    • Five healthy volunteers received clofibrate (1 g/day) for 13 days.
    • Antipyrine half-life and urinary glucaric acid excretion were measured.
    • Volunteers also received rifampicin (600 mg/day) for seven days to assess its effect on clofibrate metabolite plasma concentrations.

    Main Results:

    • Oral clofibrate administration did not significantly alter antipyrine half-life or urinary glucaric acid excretion in the volunteers.
    • Rifampicin administration led to a decrease in the plasma steady-state concentrations of chlorophenoxyisobutyric acid, a major clofibrate metabolite.
    • These findings suggest that clofibrate metabolism in humans may rely on inducible enzymatic activity.

    Conclusions:

    • Clofibrate, at the tested dosage, does not induce antipyrine metabolism or increase glucaric acid excretion in humans.
    • Rifampicin appears to induce the metabolism of clofibrate in humans, as evidenced by reduced metabolite levels.
    • Co-administration of clofibrate and rifampicin may necessitate an increased clofibrate dosage due to enhanced metabolism.

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