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Related Experiment Videos

Oral melphalan kinetics.

D S Alberts, S Y Chang, H S Chen

    Clinical Pharmacology and Therapeutics
    |December 1, 1979
    PubMed
    Summary
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    Oral melphalan bioavailability is variable and often low, impacting treatment effectiveness. This study highlights potential issues with oral melphalan absorption, suggesting bioavailability problems may cause treatment failure.

    Area of Science:

    • Pharmacokinetics
    • Oncology
    • Drug Metabolism

    Background:

    • The systemic availability of melphalan following oral administration is poorly understood.
    • Patients are frequently prescribed fixed oral melphalan dosage regimens without clear pharmacokinetic data.
    • Understanding melphalan's disposition is crucial for optimizing cancer therapy.

    Purpose of the Study:

    • To investigate the pharmacokinetic profile of melphalan after oral administration.
    • To compare the bioavailability of oral melphalan with intravenous administration.
    • To assess factors influencing melphalan absorption and excretion.

    Main Methods:

    • Pharmacokinetic study of melphalan in 14 patients receiving single oral doses.
    • Comparative analysis in 5 patients receiving both oral and intravenous melphalan (0.6 mg/kg).

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  • Measurement of plasma concentrations and urinary excretion over time.

    • Main Results:

    • Oral melphalan exhibited a mean terminal half-life of 90 ± 17 min.
    • Mean area under the plasma concentration-time curve (AUC) was 53 ± 33 µg·min/mL.
    • Oral to intravenous AUC ratio averaged 0.56, indicating significant bioavailability variability (range 0.25–0.89).
    • Urinary excretion of oral melphalan averaged 10.9 ± 4.9% in 24 hours.
    • Time to plasma appearance varied widely (15 min to 6 hr), with one case showing no detectable levels.

    Conclusions:

    • Significant inter-patient variability exists in oral melphalan absorption.
    • Inadequate oral melphalan bioavailability may contribute to treatment failure, rather than solely tumor resistance.
    • Further research into optimizing oral melphalan dosing and formulation is warranted.