Basic and clinical studies on flucytosine in patients with fungi in their urine

We studied the pharmacokinetics and clinical efficacy of flucytosine (5-FC), an antimycotic agent, in the urological field. 1) Pharmacokinetics: A single dose of 5-FC [0.5g or 1.0g (potency)] was administered to three normal adults by the cross-over method, and drug concentrations in blood and urine were measured. Three subjects also received nine consecutive 1.0 g doses of 5-FC at 12 hour intervals for administrations, and serum concentrations were measured. In the single-dose study, maximum blood levels (7.4 µg/ml at 0.5 g, 13.9 µg/ml at 1.0 g) were observed two hours after administration and the half-lives were 3.65 and 3.90 hrs, respectively. Cumulative urinary recovery rates were 87.2% and 79.8%, respectively. In the multiple-dose study, steady-state blood concentrations were obtained after the third dose and no tendency to accumulate was observed. 2) Clinical study: We treated 25 patients with fungi in their urine with 5-FC at dose of 1.0 g t.i. d. for 7–14 days. According to the criteria Japanese U TI Committee, with a slight modification, the overall clinical efficacy rate was 77.8% (14/18). Mycologically, 15 out of 20 strains (75.0%). were eradicated. Nausea and anorexia were noted in 1 patient each, but they improved without therapy. Concerning the laboratory findings, a transient elevation of ALP and Cr, and a mild decrease in K were noted in 1 patient each. Consequently, 5-FC appears to be a useful drug in the treatment of fungi in the urine.