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The kinetics of uptake of 5-fluorouracil by rat liver

L S Hsu

    British Journal of Pharmacology
    |November 1, 1982
    PubMed

    Insights

    Rat liver slices show that 5-fluorouracil (5-FU) uptake follows Michaelis-Menton kinetics, indicating a saturable, energy-dependent transport process. Non-fasting conditions enhance 5-FU uptake significantly.

    Area of Science:

    • Pharmacokinetics
    • Drug Metabolism
    • Hepatology

    Background:

    • 5-fluorouracil (5-FU) is a widely used chemotherapeutic agent.
    • Understanding its hepatic uptake mechanism is crucial for optimizing treatment.
    • Previous studies have not fully elucidated the kinetics and energy dependence of 5-FU liver transport.

    Purpose of the Study:

    • To investigate the kinetic parameters of 5-fluorouracil (5-FU) uptake by rat liver slices.
    • To determine whether 5-FU transport into liver cells is an energy-dependent process.
    • To assess the influence of physiological conditions (fasting state) on 5-FU uptake.

    Main Methods:

    • Incubation of rat liver slices (15-30 mg) in 5-fluorouracil (5-FU) solutions at 37°C.
    • Quantification of intracellular 5-FU using high-pressure liquid chromatography (HPLC).
    • Kinetic analysis (Michaelis-Menton) and assessment of transport inhibition (2,4-dinitrophenol).

    Main Results:

    • 5-FU uptake exhibited Michaelis-Menton kinetics with Kt = 15.39 mmol/L and Vmax = 1.96 µmol/g/min.
    • Transport was saturable, and uptake was significantly higher in non-fasting rats.
    • 2,4-Dinitrophenol significantly inhibited 5-FU transport, suggesting an energy requirement.
    • Intracellular 5-FU concentrations approached extracellular levels but did not significantly exceed them within 24 minutes.

    Conclusions:

    • Hepatic uptake of 5-fluorouracil (5-FU) in rats is mediated by a saturable, energy-dependent transport system.
    • Non-fasting status enhances 5-FU liver uptake.
    • These findings have implications for understanding 5-FU pharmacokinetics and potential drug interactions.

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