INDIVIDUALIZATION OF 5-FLUOROCYTOSINE THERAPY

Using a convenient and fast HPLC procedure we determined serum concent rations of the fungistatic agent 5-fluorocytosine (5-FC) in 375 sample s from 60 patients treated with this drug. The mean trough concentrati on (n = 127) was 64.3 mg/l (range: 11.8-208.0 mg/l), the mean peak con centration (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: 10.5-2 68.0 mg/l). Totally 134 (35.7%) samples were outside the therapeutic r ange (25-100 mg/l), 108 (28.8%) being too high, 26 (6.9%) being too lo w. 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 dosag e adaptation. The mean absolute prediction error of the dosage adaptat ion was +0.7 mg/l (range: -26.0 to +28.0 mg/l). The root mean square p rediction 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 t hat 5-FC monitoring is important. The applied pharmacokinetic method a llows individual adaptations of 5-FC dosage with a clinically acceptab le prediction error.