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Impaired oxidation of debrisoquine in patients with perhexiline liver injury

M Y Morgan, R Reshef, R R Shah

    Gut
    |October 1, 1984
    PubMed

    Insights

    Perhexiline maleate, an antianginal drug, can cause liver damage. Patients with this liver injury often have a genetically determined defect in drug oxidation, suggesting a hereditary predisposition.

    Area of Science:

    • Pharmacology
    • Hepatology
    • Genetics

    Background:

    • Perhexiline maleate is an antianginal medication eliminated via hepatic oxidation.
    • Adverse effects include peripheral neuropathy and liver damage.
    • A genetic basis for impaired drug oxidation is known in perhexiline-induced neuropathy.

    Observation:

    • Drug oxidation capacity was assessed in four patients with perhexiline liver injury.
    • A control group of 70 patients with chronic liver disease was included.
    • Oxidation phenotyping was used to measure metabolic drug oxidation.

    Findings:

    • All four patients with perhexiline liver damage exhibited significant metabolic defects.
    • 75% of these patients (3/4) had a genetically determined impairment in oxidation capacity.
    • Impaired oxidation was significantly more common in the perhexiline liver injury group (75%) compared to chronic liver disease patients (8.6%) and the general population (9%).

    Implications:

    • A strong association exists between perhexiline-induced liver injury and reduced drug metabolic activity.
    • The susceptibility to developing perhexiline liver injury appears to be, at least partly, genetically determined.
    • This suggests a role for genetic screening in patients prescribed perhexiline maleate.

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