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Quinine disposition kinetics.

N J White, P Chanthavanich, S Krishna

    British Journal of Clinical Pharmacology
    |October 1, 1983
    PubMed
    Summary
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    Intravenous quinine dihydrochloride administration caused significant electrocardiographic changes, including QRS and QT interval prolongation, in healthy volunteers. These effects were transient, with plasma concentrations and ECG intervals returning to baseline levels post-infusion.

    Area of Science:

    • Pharmacology
    • Cardiology
    • Clinical Trials

    Background:

    • Quinine is an antimalarial drug with known cardiac effects.
    • Understanding quinine's pharmacokinetics and pharmacodynamics is crucial for safe clinical use.

    Purpose of the Study:

    • To evaluate the cardiovascular effects of intravenous quinine dihydrochloride.
    • To determine the pharmacokinetic profile of quinine following intravenous administration.

    Main Methods:

    • Seven healthy male volunteers received intravenous quinine dihydrochloride (5 mg/kg over 5 min).
    • Electrocardiograms (ECG) were monitored for changes in QRS and QT intervals.
    • Plasma quinine concentrations were measured using spectrophotofluorimetry.
    • Pharmacokinetic analysis was performed using a two-compartment open model.

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    Main Results:

    • Minor subjective symptoms were reported, but no significant changes in pulse or blood pressure were observed.
    • Significant prolongation of QRS and rate-corrected QT intervals occurred, peaking 1-4 minutes post-infusion.
    • Peak plasma quinine concentration was 5.1 ± 1.3 mg/L.
    • Key pharmacokinetic parameters included a distribution half-time of 1.89 ± 0.54 min and an elimination half-time of 11.1 ± 2.1 h.

    Conclusions:

    • Intravenous quinine dihydrochloride causes transient but significant electrocardiographic changes in healthy individuals.
    • The drug exhibits a rapid distribution and a prolonged elimination half-life.
    • These findings highlight the importance of cardiac monitoring during quinine therapy.