European Journal of Clinical Pharmacology

, Volume 30, Issue 2, pp 231–238 | Cite as

Renal excretion and pharmacokinetics of methotrexate and 7-hydroxy-methotrexate following a 24-h high dose infusion of methotrexate in children

  • B. Winograd
  • R. J. J. Lippens
  • M. J. M. Oosterbaan
  • M. J. M. Dirks
  • T. B. Vree
  • E. van der Kleijn
Article

Summary

In children with lymphoid malignancies 18 courses of methotrexate (18–200 mg/kg) administered as a 24-h infusion were monitored. Plasma concentrations and renal excretion rates of methotrexate (MTX) and 7-hydroxymethotrexate (7-OHMTX) were determined. A low correlation was found between the administered dose of MTX and the body exposure to MTX or 7-OHMTX. Although 84% of the MTX eventually recovered from the urine was excreted during the 24 h of the infusion, the renal clearance of MTX was markedly lower during the time of the infusion than after it. There were courses with a low and others with a high renal clearance of MTX during the infusion, despite the same urine flow. A low MTX renal clearance was correlated with a high body exposure to MTX. As the same variations were also seen in the same patient during successive courses, pharmacokinetical characterization of patients appears questionable. The renal clearance of 7-OHMTX was significantly lower than the renal clearance of MTX, and the body exposure to 7-OHMTX ranged from 2–40% of the MTX body exposure. Treatment courses with a low or a high body exposure to 7-OHMTX were not associated with different urinary recoveries of the metabolite.

Differences in MTX hydroxylation could not be substantiated. Because the concentration of 7-OHMTX is high soon after the end of an infusion, a specific method of MTX determination should be chosen for controlling treatment.

Key words

methotrexate hydroxymethotrexate lymphoid malignancy renal excretion metabolism pharmacokinetics 

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Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • B. Winograd
    • 1
    • 3
  • R. J. J. Lippens
    • 2
  • M. J. M. Oosterbaan
    • 1
  • M. J. M. Dirks
    • 1
  • T. B. Vree
    • 1
  • E. van der Kleijn
    • 1
  1. 1.Departments of Clinical PharmacyUniversity of NijmegenNijmegenThe Netherlands
  2. 2.Pediatrics St. RadboudziekenhuisUniversity of NijmegenNijmegenThe Netherlands
  3. 3.Department of OncologyFree University HospitalAmsterdamThe Netherlands

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