Pharmaceutisch Weekblad

, Volume 7, Issue 4, pp 158–162 | Cite as

Comparison of linear and tapered intravenous infusion of methotrexate in oncochemotherapy. A theoretical approach

  • E. F. S. Termond
  • B. Zonnenberg
  • B. Winograd
  • M. J. M. Oosterbaan
  • E. van der Kleijn
  • T. B. Vree
Original Articles
  • 16 Downloads

Abstract

In oncochemotherapy with methotrexate (MTX) a peripheral concentration >0.45 mg/l and a plasma concentration <45 mg/l must be maintained for 20 h. The time periods required to reach and maintain steady-state concentrations after tapered and linear intravenous infusion were compared. Pharmacokinetic analyses according to a two-compartment model were used to calculate dosage regimens and concentration profiles by means of the Bayesian General Modelling Program (BM) and NONLIN. When the dosage regimen is based on a steady-state concentration in the peripheral compartment (which is the target compartment for MTX) tapered infusion reaches this concentration 40% faster and maintains it 12.5% longer, but no difference is found if the dosage regimen is based on a steady-state concentration in the central compartment. In theory the two-step 24-hour tapered infusion can be replaced by a bolus injection plus linear infusion in the ratio 1∶2 of the total dose. These dosage regimens are to be preferred over linear infusion.

Keywords

Methotrexate Total Dose Concentration Profile Dosage Regimen Theoretical Approach 

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Copyright information

© Bohn, Scheltema & Holkema 1985

Authors and Affiliations

  • E. F. S. Termond
    • 1
  • B. Zonnenberg
    • 2
  • B. Winograd
    • 3
  • M. J. M. Oosterbaan
    • 1
  • E. van der Kleijn
    • 1
  • T. B. Vree
    • 1
  1. 1.Department of Clinical Pharmacy, St. Radboud HospitalCatholic University of NijmegenHB NijmegenThe Netherlands
  2. 2.Department of Oncology, St. Radboud HospitalCatholic University of NijmegenHB NijmegenThe Netherlands
  3. 3.Department of Oncology, Medical FacultyFree University of Amsterdam (VU)BT AmsterdamThe Netherlands

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