Journal of Antimicrobial Chemotherapy (2000) 46, 171-179
© 2000 The British Society for Antimicrobial Chemotherapy
Reviews |
Flucytosine: a review of its pharmacology, clinical indications, pharmacokinetics, toxicity and drug interactions
a Departments of Clinical Pharmacy and b Medical Microbiology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Flucytosine (5-FC) is a synthetic antimycotic compound, first synthesized in 1957. It has no intrinsic antifungal capacity, but after it has been taken up by susceptible fungal cells, it is converted into 5-fluorouracil (5-FU), which is further converted to metabolites that inhibit fungal RNA and DNA synthesis. Monotherapy with 5-FC is limited because of the frequent development of resistance. In combination with amphotericin B, 5-FC can be used to treat severe systemic mycoses, such as cryptococcosis, candidosis, chromoblastomycosis and aspergillosis. Recently, 5-FC has been combined with newer azole antifungal agents; it also plays an important role in a new approach to the treatment of cancer. The severe side effects of 5-FC include hepatotoxicity and bone-marrow depression. In most patients, these side effects are concentration dependent, predictable, possibly avoidable with close monitoring to maintain 5-FC concentrations at <100 mg/L, and reversible with drug discontinuation or reduction of dose. 5-FC is well absorbed after oral administration, penetrates into body tissues well and is excreted mainly by the kidneys. In renal failure, major dose adjustments have to be made. The most important drug interaction of 5-FC occurs with concomitant administration of 5-FC and nephrotoxic drugs, especially amphotericin B. Owing to the crucial role of glomerular filtration in 5-FC elimination, drugs that impair this mechanism will decrease the elimination of 5-FC and thus prolong its half-life.
* Corresponding author. Tel: +31-20-566-3474; Fax: +31-20-697-2291; E-mail: h.j.guchelaar{at}amc.uva.nl
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Florent, T. Noel, G. Ruprich-Robert, B. Da Silva, V. Fitton-Ouhabi, C. Chastin, N. Papon, and F. Chapeland-Leclerc Nonsense and Missense Mutations in FCY2 and FCY1 Genes Are Responsible for Flucytosine Resistance and Flucytosine-Fluconazole Cross-Resistance in Clinical Isolates of Candida lusitaniae Antimicrob. Agents Chemother., July 1, 2009; 53(7): 2982 - 2990. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Murphy, J. M. Bolduc, J. L. Gallaher, B. L. Stoddard, and D. Baker Alteration of enzyme specificity by computational loop remodeling and design PNAS, June 9, 2009; 106(23): 9215 - 9220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. E. Verweij, D. T. A. Te Dorsthorst, W. H. P. Janssen, J. F. G. M. Meis, and J. W. Mouton In Vitro Activities at pH 5.0 and pH 7.0 and In Vivo Efficacy of Flucytosine against Aspergillus fumigatus Antimicrob. Agents Chemother., December 1, 2008; 52(12): 4483 - 4485. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Goodwin and R. H. Drew Antifungal serum concentration monitoring: an update J. Antimicrob. Chemother., January 1, 2008; 61(1): 17 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Rhome, T. McQuiston, T. Kechichian, A. Bielawska, M. Hennig, M. Drago, G. Morace, C. Luberto, and M. Del Poeta Biosynthesis and Immunogenicity of Glucosylceramide in Cryptococcus neoformans and Other Human Pathogens Eukaryot. Cell, October 1, 2007; 6(10): 1715 - 1726. [Full Text] [PDF]
|
|
|
|
|
|
P. H. J. van der Voort, E. C. Boerma, and J. P. Yska Serum and intraperitoneal levels of amphotericin B and flucytosine during intravenous treatment of critically ill patients with Candida peritonitis J. Antimicrob. Chemother., May 1, 2007; 59(5): 952 - 956. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Bourbeau, C. J. Lau, J. Jaime, Z. Koty, S. P. Zehntner, G. Lavoie, A.-M. Mes-Masson, J. Nalbantoglu, and B. Massie Improvement of Antitumor Activity by Gene Amplification with a Replicating but Nondisseminating Adenovirus Cancer Res., April 1, 2007; 67(7): 3387 - 3395. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Pfaller and D. J. Diekema Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem Clin. Microbiol. Rev., January 1, 2007; 20(1): 133 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Papon, T. Noel, M. Florent, S. Gibot-Leclerc, D. Jean, C. Chastin, J. Villard, and F. Chapeland-Leclerc Molecular Mechanism of Flucytosine Resistance in Candida lusitaniae: Contribution of the FCY2, FCY1, and FUR1 Genes to 5-Fluorouracil and Fluconazole Cross-Resistance Antimicrob. Agents Chemother., January 1, 2007; 51(1): 369 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Beumer, J. L. Eiseman, R. A. Parise, E. Joseph, J. L. Holleran, J. M. Covey, and M. J. Egorin Pharmacokinetics, Metabolism, and Oral Bioavailability of the DNA Methyltransferase Inhibitor 5-Fluoro-2'-Deoxycytidine in Mice Clin. Cancer Res., December 15, 2006; 12(24): 7483 - 7491. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-S. Shieh, A.-L. Shiau, Y.-T. Yo, P.-R. Lin, C.-C. Chang, T.-S. Tzai, and C.-L. Wu Low-Dose Etoposide Enhances Telomerase-Dependent Adenovirus-Mediated Cytosine Deaminase Gene Therapy through Augmentation of Adenoviral Infection and Transgene Expression in a Syngeneic Bladder Tumor Model. Cancer Res., October 15, 2006; 66(20): 9957 - 9966. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Meletiadis, S. Chanock, and T. J. Walsh Human Pharmacogenomic Variations and Their Implications for Antifungal Efficacy Clin. Microbiol. Rev., October 1, 2006; 19(4): 763 - 787. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Enoch, H. A. Ludlam, and N. M. Brown Invasive fungal infections: a review of epidemiology and management options. J. Med. Microbiol., July 1, 2006; 55(Pt 7): 809 - 818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Schwarz, F. Dromer, O. Lortholary, and E. Dannaoui Efficacy of Amphotericin B in Combination with Flucytosine against Flucytosine-Susceptible or Flucytosine-Resistant Isolates of Cryptococcus neoformans during Disseminated Murine Cryptococcosis Antimicrob. Agents Chemother., January 1, 2006; 50(1): 113 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. T. A. te Dorsthorst, P. E. Verweij, J. F. G. M. Meis, and J. W. Mouton Efficacy and Pharmacodynamics of Flucytosine Monotherapy in a Nonneutropenic Murine Model of Invasive Aspergillosis Antimicrob. Agents Chemother., October 1, 2005; 49(10): 4220 - 4226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Chapeland-Leclerc, J. Bouchoux, A. Goumar, C. Chastin, J. Villard, and T. Noel Inactivation of the FCY2 Gene Encoding Purine-Cytosine Permease Promotes Cross-Resistance to Flucytosine and Fluconazole in Candida lusitaniae Antimicrob. Agents Chemother., August 1, 2005; 49(8): 3101 - 3108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Lewin III, M. Lapointe, and W. C. Ziai Central Nervous System Infections in the Critically Ill Journal of Pharmacy Practice, February 1, 2005; 18(1): 25 - 41. [Abstract] [PDF]
|
|
|
|
|
|
W. W. Hope, L. Tabernero, D. W. Denning, and M. J. Anderson Molecular Mechanisms of Primary Resistance to Flucytosine in Candida albicans Antimicrob. Agents Chemother., November 1, 2004; 48(11): 4377 - 4386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. T. A. Te Dorsthorst, P. E. Verweij, J. F. G. M. Meis, N. C. Punt, and J. W. Mouton In Vitro Interactions between Amphotericin B, Itraconazole, and Flucytosine against 21 Clinical Aspergillus Isolates Determined by Two Drug Interaction Models Antimicrob. Agents Chemother., June 1, 2004; 48(6): 2007 - 2013. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Dannaoui, O. Lortholary, and F. Dromer In Vitro Evaluation of Double and Triple Combinations of Antifungal Drugs against Aspergillus fumigatus and Aspergillus terreus Antimicrob. Agents Chemother., March 1, 2004; 48(3): 970 - 978. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Noel, F. Francois, P. Paumard, C. Chastin, D. Brethes, and J. Villard Flucytosine-Fluconazole Cross-Resistance in Purine-Cytosine Permease-Deficient Candida lusitaniae Clinical Isolates: Indirect Evidence of a Fluconazole Uptake Transporter Antimicrob. Agents Chemother., April 1, 2003; 47(4): 1275 - 1284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. B. Moore, C. M. Walls, and D. W. Denning Comparison of three methods for in vitro susceptibility testing of Candida species with flucytosine J. Antimicrob. Chemother., February 1, 2003; 51(2): 297 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Pfaller, S. A. Messer, L. Boyken, H. Huynh, R. J. Hollis, and D. J. Diekema In Vitro Activities of 5-Fluorocytosine against 8,803 Clinical Isolates of Candida spp.: Global Assessment of Primary Resistance Using National Committee for Clinical Laboratory Standards Susceptibility Testing Methods Antimicrob. Agents Chemother., November 1, 2002; 46(11): 3518 - 3521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. T. A. Te Dorsthorst, P. E. Verweij, J. Meletiadis, M. Bergervoet, N. C. Punt, J. F. G. M. Meis, and J. W. Mouton In Vitro Interaction of Flucytosine Combined with Amphotericin B or Fluconazole against Thirty-Five Yeast Isolates Determined by both the Fractional Inhibitory Concentration Index and the Response Surface Approach Antimicrob. Agents Chemother., September 1, 2002; 46(9): 2982 - 2989. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Miller, C. R. Williams, D. J. Buchsbaum, and G. Y. Gillespie Intratumoral 5-Fluorouracil Produced by Cytosine Deaminase/5-Fluorocytosine Gene Therapy Is Effective for Experimental Human Glioblastomas Cancer Res., February 1, 2002; 62(3): 773 - 780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Goldstein and J. H. McCusker Development of Saccharomyces cerevisiae as a Model Pathogen: A System for the Genetic Identification of Gene Products Required for Survival in the Mammalian Host Environment Genetics, October 1, 2001; 159(2): 499 - 513. [Abstract] [Full Text] [PDF]
|
|