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Diazepam/beta-adrenoceptor antagonist interactions.

G Hawksworth, T Betts, A Crowe

    British Journal of Clinical Pharmacology
    |January 1, 1984
    PubMed
    Summary
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    Lipophilic beta-blockers like metoprolol can increase diazepam levels in the body, potentially affecting its metabolism and leading to impaired kinetic visual acuity. Hydrophilic atenolol showed no significant interaction with diazepam.

    Area of Science:

    • Pharmacology
    • Clinical Pharmacy

    Background:

    • Diazepam is a widely used anxiolytic and sedative.
    • Beta-adrenoceptor antagonists (beta-blockers) are commonly prescribed for cardiovascular conditions.
    • Interactions between co-administered drugs can alter pharmacokinetic and pharmacodynamic profiles.

    Purpose of the Study:

    • To investigate the pharmacokinetic and pharmacodynamic interactions between diazepam and lipophilic (propranolol, metoprolol) versus hydrophilic (atenolol) beta-blockers.
    • To determine if beta-blocker lipophilicity influences the interaction with diazepam.

    Main Methods:

    • A randomized, placebo-controlled study involving 12 healthy subjects.
    • Administration of diazepam alone and in combination with propranolol, metoprolol, or atenolol.
    • Measurement of plasma concentrations of diazepam and its metabolite, N-desmethyldiazepam.

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  • Assessment of pharmacokinetic parameters (AUC0-8h) and pharmacodynamic effects (kinetic visual acuity).

    • Main Results:

    • Lipophilic beta-blockers (propranolol and metoprolol) caused a small but significant increase in diazepam's area under the curve (AUC0-8h), suggesting inhibited diazepam metabolism.
    • Atenolol, a hydrophilic beta-blocker, did not significantly affect diazepam pharmacokinetics.
    • Co-administration of diazepam with metoprolol resulted in a significant impairment of kinetic visual acuity compared to placebo or atenolol.
    • A correlation was observed between diazepam plasma concentrations and impaired kinetic visual acuity.

    Conclusions:

    • Lipophilic beta-blockers may inhibit diazepam metabolism, leading to increased plasma concentrations.
    • Pharmacodynamic interactions, such as impaired kinetic visual acuity, can occur when diazepam is combined with lipophilic beta-blockers, potentially beyond the observed pharmacokinetic changes.