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Enzyme induction and renal function in man

E E Ohnhaus, J Martin, J Kinser

    British Journal of Clinical Pharmacology
    |February 1, 1977
    PubMed
    Summary
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    Phenobarbital administration increased liver enzyme activity in humans, indicated by faster antipyrine metabolism. However, this did not enhance kidney function or para-aminohippuric acid (PAH) clearance, unlike in rats.

    Area of Science:

    • Pharmacology and Toxicology
    • Human Physiology
    • Drug Metabolism

    Background:

    • Previous rat studies indicated increased para-aminohippuric acid (PAH) clearance after phenobarbital administration.
    • This suggested potential effects of liver microsomal enzyme induction on renal function.

    Purpose of the Study:

    • To investigate the effect of liver microsomal enzyme induction on renal function in healthy human volunteers.
    • To determine if phenobarbital-induced enzyme activity translates to increased PAH clearance in humans.

    Main Methods:

    • Assessed liver microsomal enzyme activity using antipyrine elimination, gamma-glutamyl-transpeptidase, and D-glucaric acid excretion.
    • Measured renal function via endogenous creatinine clearance, 51Cr-EDTA, and 125I-Hippuran clearance.

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  • Administered antipyrine to a subset of volunteers to induce enzyme activity and re-evaluated parameters.

    • Main Results:

    • No correlation was observed between liver enzyme activity and renal function parameters initially.
    • Antipyrine administration significantly increased liver enzyme activity markers (decreased half-life, increased clearance, elevated GGT and D-glucaric acid).
    • Renal function parameters remained unchanged despite significant liver enzyme induction.

    Conclusions:

    • Induction of liver microsomal enzyme activity in humans does not lead to increased PAH clearance.
    • Findings contrast with previous rat studies, highlighting species-specific responses to enzyme induction.