Individualization of 5-fluorocytosine therapy

Chemotherapy. May-Jun 1994;40(3):149-56. doi: 10.1159/000239186.

Abstract

Using a convenient and fast HPLC procedure we determined serum concentrations of the fungistatic agent 5-fluorocytosine (5-FC) in 375 samples from 60 patients treated with this drug. The mean trough concentration (n = 127) was 64.3 mg/l (range: 11.8-208.0 mg/l), the mean peak concentration (n = 122) was 99.9 mg/l (range: 25.6-263.8 mg/l), the mean nonpeak/nontrough concentration (n = 126) was 80.1 mg/l (range: 10.5-268.0 mg/l). Totally 134 (35.7%) samples were outside the therapeutic range (25-100 mg/l), 108 (28.8%) being too high, 26 (6.9%) being too low. Forty-four (73%) patients showed 5-FC serum concentrations outside the therapeutic range at least once during the treatment course. In a prospective study we performed 65 dosage predictions on 30 patients by use of a 3-point method previously developed for aminoglycoside dosage adaptation. The mean absolute prediction error of the dosage adaptation was +0.7 mg/l (range: -26.0 to +28.0 mg/l). The root mean square prediction error was 10.7 mg/l. The mean predicted concentration (65.3 mg/l) agreed very well with the mean measured concentration (64.6 mg/l). The frequency distribution of 5-FC serum concentrations indicates that 5-FC monitoring is important. The applied pharmacokinetic method allows individual adaptations of 5-FC dosage with a clinically acceptable prediction error.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Analysis of Variance
  • Child
  • Chromatography, High Pressure Liquid / methods*
  • Female
  • Flucytosine / administration & dosage*
  • Flucytosine / blood
  • Flucytosine / pharmacokinetics
  • Humans
  • Infusions, Intravenous
  • Male
  • Prospective Studies
  • Reproducibility of Results

Substances

  • Flucytosine