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Diazoxide concentration-response relation in hypertension

R I Ogilvie, J H Nadeau, D S Sitar

    Hypertension (Dallas, Tex. : 1979)
    |January 1, 1982
    PubMed
    Summary
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    Diazoxide effectively lowers blood pressure in hypertensive patients. Pharmacokinetic analysis guided a dosing regimen for predictable, sustained reductions in mean arterial pressure (MAP).

    Area of Science:

    • Pharmacology
    • Clinical Hypertension
    • Drug Metabolism

    Background:

    • Essential hypertension requires effective antihypertensive agents.
    • Understanding drug pharmacokinetics is crucial for optimizing treatment.
    • Diazoxide is a vasodilator used to manage hypertensive emergencies.

    Observation:

    • Bolus infusions of diazoxide (1-4 mg/kg) were administered over 5-20 seconds to patients with stable essential hypertension.
    • Maximal reduction in mean arterial pressure (MAP) occurred within 2 minutes post-infusion.
    • A linear correlation existed between diazoxide dose/plasma concentration and MAP reduction.

    Findings:

    • Individual pharmacokinetic parameters including volume of distribution (Vdss), elimination half-life (t 1/2), and plasma clearance (Clp) were determined.

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  • Steady-state diazoxide concentrations were achieved within 0.5 hours.
  • Predicted steady-state MAP reductions ranged from 16% to 30% based on concentration-response curves.

    • Implications:

    • Kinetic principles enable the calculation of optimal loading and maintenance doses for diazoxide.
    • A proposed regimen (7.5 mg/kg load, 10% maintenance q6h) achieved predictable MAP reduction in accelerated hypertension.
    • This approach allows for controlled and individualized diazoxide therapy in hypertensive patients.