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Related Experiment Videos

Test dose for predicting high-dose methotrexate infusions.

I G Kerr, J Jolivet, J M Collins

    Clinical Pharmacology and Therapeutics
    |January 1, 1983
    PubMed
    Summary
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    Test-dose methotrexate kinetics accurately predict high-dose infusion concentrations. This method may guide dose adjustments for methotrexate (MTX) in high-risk patients, improving treatment outcomes.

    Area of Science:

    • Pharmacokinetics
    • Oncology
    • Drug Metabolism

    Background:

    • High-dose methotrexate (MTX) therapy requires careful monitoring due to its narrow therapeutic index.
    • Predicting individual patient drug concentrations is crucial for optimizing efficacy and minimizing toxicity.
    • Current methods for predicting MTX kinetics can be complex and time-consuming.

    Purpose of the Study:

    • To evaluate the utility of test-dose methotrexate (MTX) kinetics in predicting plasma drug concentrations during and after high-dose infusions.
    • To determine if individual MTX kinetics from a small test dose can guide dose modifications for moderate- and high-dose infusions.
    • To assess the correlation between MTX clearance, age, and creatinine clearance.

    Main Methods:

    • Eighteen patients received a small, non-toxic dose of MTX (10 mg/m2) followed by monitoring for 12-24 hours.

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  • Kinetic data from the test dose were used to predict MTX concentrations during subsequent moderate- to high-dose infusions (150-1500 mg/m2).
  • Plasma MTX concentrations were measured at various time points, including infusion plateau and 24 hours post-infusion.

    • Main Results:

    • MTX clearance after the test dose ranged from 36 to 138 ml/min/m2 and decreased with age (r = -0.49, P < 0.05).
    • Test-dose kinetic parameters accurately predicted infusion plateau (r = 0.89, P < 0.001) and 24-hr MTX concentrations (r = 0.92, P < 0.001).
    • No significant correlation was found between MTX clearance and creatinine clearance in patients with varying renal function (32-63 ml/min/m2).

    Conclusions:

    • Individual methotrexate (MTX) kinetics derived from a test dose can reliably predict plasma drug concentrations during high-dose infusions.
    • Test-dose MTX kinetics may serve as a valuable tool for guiding dose modifications in high-risk patients.
    • This approach offers a potential method for optimizing MTX therapy and reducing toxicity.