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4-Aminopyridine kinetics

D R Uges, Y J Sohn, B Greijdanus

    Clinical Pharmacology and Therapeutics
    |May 1, 1982
    PubMed
    Summary
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    This study investigated the pharmacokinetics of 4-aminopyridine (4-AP) in healthy subjects. Enteric-coated 4-AP tablets demonstrated good bioavailability, similar to intravenous administration.

    Area of Science:

    • Pharmacology
    • Clinical Pharmacokinetics

    Background:

    • 4-aminopyridine (4-AP) is a potassium channel blocker with therapeutic potential.
    • Understanding 4-AP pharmacokinetics is crucial for optimizing its clinical use.

    Purpose of the Study:

    • To characterize the pharmacokinetic profile of 4-aminopyridine (4-AP) following intravenous and oral administration.
    • To evaluate the bioavailability of enteric-coated 4-AP tablets.

    Main Methods:

    • Single 20-mg intravenous and oral doses of 4-AP were administered to healthy subjects.
    • Serum, saliva, and urine samples were analyzed using high-performance liquid chromatography.
    • Pharmacokinetic parameters including volume of distribution, half-life, and clearance were calculated.

    Main Results:

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    • 4-AP exhibited a triexponential or biexponential kinetic model after IV dosing.
    • Terminal half-life was approximately 3.6 hours, with a volume of distribution of 2.6 L/kg.
    • Urinary excretion of unchanged 4-AP was high (>88%), and bioavailability of enteric-coated tablets was comparable to IV administration (95%).

    Conclusions:

    • 4-aminopyridine is rapidly absorbed and extensively excreted unchanged in urine.
    • Enteric-coated 4-AP tablets offer comparable bioavailability to intravenous dosing.
    • Saliva can serve as a reliable matrix for pharmacokinetic monitoring of 4-AP.