Pharmacokinetics, outcome of treatment, and toxic effects of amphotericin B and 5-fluorocytosine in neonates

J Pediatr. 1990 May;116(5):791-7. doi: 10.1016/s0022-3476(05)82674-5.


To determine the pharmacokinetics of amphotericin B and 5-fluorocytosine in neonates, we measured serum concentrations at first dose and after 5 days of therapy by high-performance liquid chromatography in 13 neonates (mean birth weight 1.2 +/- 0.8 kg). The dose of amphotericin B was serially increased from 0.1 to 0.5 mg/kg/day in 10 infants but was decreased from 0.8 to 1.0 to 0.5 mg/kg/day in three infants. Amphotericin B concentrations were not detectable in infants receiving 0.1 mg/kg/day. Amphotericin B cerebrospinal fluid concentrations were 40% to 90% of serum values obtained simultaneously. Serum concentrations after oral administration of 5-fluorocytosine (dose 25 to 100 mg/kg/day) were detectable in all infants. We found extreme interindividual variability for the half-life, volume of distribution, and clearance for both drugs. Four infants had minimal elimination for both drugs between doses, a finding that correlates with rises in serum creatinine (greater than 0.4 mg/dl, 40 mumol/L) and blood urea nitrogen (greater than 10 mg/dl, 3.6 mmol/L). We recommend that the dose of amphotericin B given on the first day of treatment be greater than the usual testing dose of 0.1 mg/kg/day. We also recommend an initial 24-hour dosing interval for amphotericin B and 5-fluorocytosine. Serum drug concentrations may need to be monitored in high-risk, low birth weight infants.

MeSH terms

  • Amphotericin B / administration & dosage
  • Amphotericin B / blood
  • Amphotericin B / pharmacokinetics*
  • Amphotericin B / therapeutic use
  • Amphotericin B / toxicity
  • Candidiasis / drug therapy
  • Flucytosine / administration & dosage
  • Flucytosine / blood
  • Flucytosine / pharmacokinetics*
  • Flucytosine / therapeutic use
  • Flucytosine / toxicity
  • Gestational Age
  • Humans
  • Infant, Low Birth Weight / metabolism*
  • Infant, Newborn
  • Infant, Premature / metabolism*
  • Kidney / drug effects
  • Mycoses / drug therapy*
  • Prognosis


  • Amphotericin B
  • Flucytosine