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Related Experiment Videos

Lorcainide disposition kinetics in arrhythmia patients.

R E Kates, D L Keefe, R A Winkle

    Clinical Pharmacology and Therapeutics
    |January 1, 1983
    PubMed
    Summary

    This study investigated lorcainide pharmacokinetics in patients with ventricular arrhythmias. Lorcainide clearance appears to decrease with prolonged oral dosing, impacting drug accumulation.

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    Area of Science:

    • Pharmacology
    • Clinical Pharmacy
    • Cardiology

    Background:

    • Ventricular arrhythmias require effective antiarrhythmic drug therapy.
    • Understanding drug disposition kinetics is crucial for optimizing treatment.
    • Lorcainide is an antiarrhythmic agent whose long-term pharmacokinetic profile requires elucidation.

    Purpose of the Study:

    • To characterize the disposition kinetics of lorcainide following intravenous and oral administration.
    • To evaluate the pharmacokinetic behavior of lorcainide and its active metabolite, norlorcainide, during long-term oral dosing.
    • To identify potential changes in lorcainide clearance over time.

    Main Methods:

    • Intravenous and oral administration of lorcainide to patients with ventricular arrhythmias.
    • Plasma lorcainide concentrations determined by high-pressure liquid chromatography.
    • Pharmacokinetic data analyzed using a three-compartment model.
    • Model-independent pharmacokinetic parameters calculated.

    Main Results:

    • Intravenous lorcainide (100-200 mg) exhibited clearance of 14.4 mL/min/kg, volume of distribution of 6.33 L/kg, and half-life of 7.8 hours.
    • After oral dosing (100 mg q12h), lorcainide and norlorcainide half-lives were 9.6 and 26.8 hours, respectively.
    • Steady-state norlorcainide levels were approximately 2.2 times higher than lorcainide levels.
    • A decrease in lorcainide clearance was observed during long-term dosing.

    Conclusions:

    • Lorcainide exhibits complex disposition kinetics, influenced by administration route and duration.
    • The active metabolite, norlorcainide, accumulates significantly during chronic oral therapy.
    • Reduced lorcainide clearance over time suggests potential for drug accumulation and warrants careful monitoring in patients with ventricular arrhythmias.

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