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Interaction between oral propranolol and hydralazine

A J McLean, H Skews, A Bobik

    Clinical Pharmacology and Therapeutics
    |June 1, 1980
    PubMed
    Summary
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    Oral hydralazine increases propranolol (a beta-blocker) absorption by affecting liver metabolism. This suggests fixed dosing schedules are needed to avoid unpredictable propranolol drug levels.

    Area of Science:

    • Pharmacology
    • Drug Metabolism
    • Clinical Pharmacy

    Background:

    • Propranolol is a high-clearance drug subject to significant first-pass hepatic metabolism.
    • Hydralazine is an antihypertensive agent that may influence hepatic drug metabolism or splanchnic blood flow.

    Purpose of the Study:

    • To investigate the effect of oral hydralazine on the pharmacokinetics of oral propranolol in healthy subjects.
    • To determine if hydralazine alters propranolol's systemic availability by affecting its first-pass metabolism.

    Main Methods:

    • Seven healthy volunteers received propranolol (1 mg/kg) alone and with varying doses of hydralazine (25, 50, 100 mg) in a crossover design.
    • Plasma concentrations of propranolol were measured over time.
    • Urinary recovery of radiolabeled propranolol and metabolites was assessed.

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  • Systemic clearance and bioavailability of propranolol were calculated.

    • Main Results:

    • Hydralazine significantly increased peak plasma concentrations and the area under the propranolol concentration-time curve.
    • No significant changes were observed in the urinary recovery of propranolol or its metabolites.
    • Systemic clearance of propranolol remained unchanged, indicating enhanced bioavailability due to reduced first-pass metabolism.

    Conclusions:

    • Oral hydralazine enhances the systemic availability of propranolol by reducing its first-pass hepatic clearance.
    • This interaction highlights the potential for drugs affecting hepatic extraction to cause significant variability in propranolol plasma concentrations.
    • Co-administration of propranolol with hydralazine, or other drugs affecting first-pass metabolism, requires careful consideration of dosing to avoid unpredictable drug levels.