Individualization of 5-fluorocytosine therapy.
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.
Petersen
D
D
Institut für Klinische Chemie I, Medizinische Hochschule Hannover, FRG.
Demertzis
S
S
Freund
M
M
Schumann
G
G
Oellerich
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002648:Child; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D005437:Flucytosine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D011446:Prospective Studies; D015203:Reproducibility of Results
D005437:Flucytosine