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Diazepam interaction with antituberculosis drugs

H R Ochs, D J Greenblatt, G M Roberts

    Clinical Pharmacology and Therapeutics
    |May 1, 1981
    PubMed
    Summary
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    Antituberculosis drugs affect diazepam metabolism. Isoniazid alone prolongs diazepam

    Area of Science:

    • Pharmacokinetics
    • Pharmacology
    • Drug Interactions

    Background:

    • Antituberculosis drugs are essential for treating tuberculosis.
    • Diazepam is a commonly prescribed benzodiazepine.
    • Potential drug interactions between antituberculosis agents and diazepam require investigation.

    Purpose of the Study:

    • To assess the influence of antituberculosis drugs on diazepam disposition.
    • To evaluate how isoniazid (INH) alone affects diazepam pharmacokinetics.
    • To determine the impact of triple therapy (INH, ethambutol, rifampin) on diazepam pharmacokinetics.

    Main Methods:

    • Single intravenous doses of diazepam administered to healthy volunteers and tuberculosis patients.
    • Study 1: Diazepam disposition assessed in healthy subjects with and without isoniazid (180 mg/day).

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  • Study 2: Diazepam disposition compared between tuberculosis patients on triple therapy and healthy controls.
  • Study 3: Diazepam disposition compared between tuberculosis patients on ethambutol alone and controls.

    • Main Results:

    • Isoniazid alone prolonged diazepam's elimination half-life (t1/2) and reduced its clearance.
    • Tuberculosis patients on triple therapy exhibited significantly shorter diazepam t1/2 and increased clearance compared to controls.
    • Ethambutol alone showed no statistically significant impact on diazepam disposition.

    Conclusions:

    • Isoniazid impairs diazepam clearance and prolongs its half-life.
    • Rifampin in triple therapy likely induces enzymes, leading to increased diazepam clearance and shortened half-life.
    • Diazepam dosage adjustments may be necessary for tuberculosis patients undergoing chemotherapy.