Pharmacological studies with 5-fluorocytosine.
A cylinder plate bioassay for 5-fluorocytosine (5-FC) is described which permits determination of 5-FC concentrations in biological fluids in the presence of amphotericin B. Using this assay, we determined serum concentrations in 12 patients after a single dose of drug and in 8 patients receiving daily 5-FC at 6-hr intervals (4 to 120 days). Drug was detectable in serum as early as 0.5 hr and concentrations were measurable as long as 24 hr after a dose, regardless of renal function. Peak concentrations occurred 6 hr after the initial drug dose, but were seen between 1 and 2 hr after a dose in all patients receiving a minimum of 4 days of therapy. Mild to moderate renal impairment produced marked increases in peak 5-FC concentrations in the serum of a group of eight patients on three different dosage schedules. Five patients were studied before and after amphotericin B-induced renal insufficiency. Peak concentrations increased from 14 to 142% concomitant with the change in renal function. Parallel studies in rabbits confirmed the results in our patients. 5-FC half-life in the serum of 10 rabbits increased from 3.35 +/- 0.27 to 24.63 +/- 0.70 hr after experimentally induced acute renal failure. Concentrations of 5-FC in the cerebrospinal fluid of five patients ranged from 17 to 62 mug/ml and were 74.4 +/- 5.6% of simultaneously determined serum concentrations. The effect of renal function on 5-FC concentrations in cerebrospinal fluid was similar to that seen with serum.
D000328:Adult; D000818:Animals; D001681:Biological Assay; D003596:Cytosine / Q000031:analogs & derivatives*; D005260:Female; D005437:Flucytosine / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D011817:Rabbits
D003596:Cytosine; D005437:Flucytosine