Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Flucytosine is a broad-spectrum antifungal agent generally used in combined therapy (often with amphotericin B) for treatment of fungal infections such as cryptococcal meningitis. Concerns with toxicity (bone marrow suppression, hepatic dysfunction) and development of fungal resistance limit the use of flucytosine, particularly as a monotherapy. The drug is well-absorbed orally, but can also be administered intravenously (available outside of the United States).
There is good correlation between serum concentrations of flucytosine with both efficacy and risk for toxicity. Because of the drugs short half-life (3-6 hours), therapeutic monitoring is typically performed at peak levels, 1 to 2 hours after an oral dose or 30 minutes after an intravenous administration.
Flucytosine is eliminated primarily as unmetabolized drug in urine. Patients with renal dysfunction may require dose adjustments or more frequent monitoring to ensure that serum concentrations do not accumulate to excessive levels. Nephrotoxicity associated with use of amphotericin B can affect elimination of flucytosine when the drugs are coadministered.
Monitoring serum concentration during therapy
Evaluating potential toxicity
May be useful to evaluate patient compliance
Most individuals display optimal response to flucytosine when peak serum levels (1-2 hours after oral dosing) are greater than 25.0 mcg/mL. Some infections may require higher concentrations for efficacy. Toxicity is more likely when peak serum concentrations are greater than 100.0 mcg/mL
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test cannot be performed on whole blood. Serum must be separated from cells within 2 hours of draw.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Peak >25.0 mcg/mL (difficult infections may require higher concentrations)
Peak >100.0 mcg/mL
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Goodwin ML, Drew RH: Antifungal serum concentration monitoring: an update. J Antimicrob Chemother 2008;61:17-25
2. Andes D, Pascual A, Marchetti O: Antifungal therapeutic drug monitoring: established and emerging indications. Antimicrob Agents Chemother 2009;53(1):24-34