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Related Experiment Videos

Theoretically required urinary flow during high-dose methotrexate infusion.

K Sasaki, J Tanaka, T Fujimoto

    Cancer Chemotherapy and Pharmacology
    |January 1, 1984
    PubMed
    Summary
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    High-dose methotrexate (H-D-MTX) can exceed solubility limits, necessitating careful monitoring of renal excretion. Understanding theoretically required urinary flow (TRUF) is crucial for safe H-D-MTX administration in pediatric oncology.

    Area of Science:

    • Pharmacology
    • Pediatric Oncology
    • Nephrology

    Background:

    • High-dose methotrexate (H-D-MTX) is a critical chemotherapy agent used in pediatric malignancies.
    • Renal excretion is the primary route for eliminating MTX and its metabolite, 7-hydroxymethotrexate (7-OH-MTX).
    • Understanding excretion dynamics is vital for preventing MTX toxicity.

    Purpose of the Study:

    • To analyze the renal excretion of methotrexate (MTX) and 7-hydroxymethotrexate (7-OH-MTX) in children receiving H-D-MTX.
    • To determine the theoretically required urinary flow (TRUF) for safe MTX clearance.
    • To correlate TRUF with MTX dosage and urinary pH.

    Main Methods:

    • Analysis of renal excretion of MTX and 7-OH-MTX in 12 pediatric cancer patients during 52 H-D-MTX courses.

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  • Dosages ranged from 0.7 to 8.4 g/m2.
  • Estimation of TRUF based on MTX and metabolite excretion and solubility at different pH levels.

    • Main Results:

    • Peak MTX and 7-OH-MTX concentrations exceeded aqueous solubility at pH ≤ 6.0.
    • Cumulative urinary excretion was 75%-98% for MTX and 3%-15% for 7-OH-MTX.
    • TRUF increased significantly with decreasing urinary pH and increasing MTX dosage.

    Conclusions:

    • H-D-MTX administration requires attention to urinary pH to prevent precipitation and toxicity.
    • TRUF is a critical parameter for guiding hydration and alkalinization strategies during H-D-MTX therapy.
    • Optimizing urinary flow and pH is essential for safe and effective MTX treatment in children.