Flucytosine and Amphotericin B: Hemodialysis Effects on the Plasma Concentration and Clearance

The efficacy of hemodialysis in removing flucytosine (5-fluorocytosine) and amphotericin B from blood was studied in eight adult patients with renal failure who required chronic hemodialysis; the results were correlated with the protein-binding of these drugs. Creatinine, flucytosine, and amphotericin B concentrations were measured immediately before and after dialysis, as well as in arterial samples of blood entering and leaving the artificial kidney after 2, 4, or 6 hours of hemodialysis. Clearances of flucytosine and creatinine by the artificial kidney were indistinguishable, and both increased linearly with blood flow through the dialyzer. These results were consistent with the minimal protein-binding (< 5%) found in vitro. In contrast to flucytosine, amphotericin B was highly (> 90%) protein-bound, poorly dialyzable, and the clearance rate by the artificial kidney ranged from 3% to 15% of that for creatinine. From these data, recommended dosage schedules for flucytosine and amphotericin B, when used to treat fungal infections in patients undergoing hemodialysis, were developed.