title: Evidence of excessive concentrations of 5-flucytosine in children aged below 12 years: a 12-year review of serum concentrations from a UK clinical assay reference laboratory.
abstract: 5-flucytosine (5-FC) is an antifungal drug used for the treatment of serious infections caused by Candida or Cryptococcus spp. In the UK, the recommended pre- and post-dose serum therapeutic ranges are 30-40 mg/L and 70-80 mg/L, respectively. A 12-year retrospective review of serum concentrations of 5-FC in three groups of children aged 1-30 days (n=167), 31-60 days (n=102) and 91 days to 12 years (n=122) was conducted. In these three age groups, 65.1%, 44.4% and 21.3% of pre-dose samples and 39.3%, 29.2% and 19.7% of post-dose samples were above the recommended ranges. Both the mean concentration and the percentage of concentrations above the recommended ranges were significantly higher in the youngest age group (1-30 days old), suggesting that the standard dose of 100 mg/kg daily may not be an appropriate dose in this age group.
authors.affiliation: Bristol Centre for Antimicrobial Research and Evaluation, Department of Medical Microbiology, Southmead Hospital, North Bristol Trust, Bristol, UK. mehnamsoltani@yahoo.com
authors.forename: Mehnam
authors.initials: M
authors.lastname: Soltani
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Tobin
authors.forename: Karen E
authors.initials: KE
authors.lastname: Bowker
authors.forename: Julie
authors.initials: J
authors.lastname: Sunderland
authors.forename: Alasdair P
authors.initials: AP
authors.lastname: MacGowan
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lovering
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D016903:Drug Monitoring; D005437:Flucytosine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007753:Laboratories; D009181:Mycoses / Q000188:drug therapy; D012015:Reference Standards; D006113:United Kingdom
chemical_list: D000935:Antifungal Agents; D005437:Flucytosine