Cited by 184Antifungal resistance and susceptibilityPharmaceutical studies and practicesFungal Infections and Studies

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

Baley, Jill E., Meyers, Carolyn, Kliegman, Robert M., Jacobs, Michael R., Blumer, Jeffrey L.·1990·The Journal of Pediatrics

DOI 10.1016/s0022-3476(05)82674-5

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Abstract

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.

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Authors: Baley, J. E., Meyers, C., Kliegman, R. M., Jacobs, M. R., & Blumer, J. L.
Affiliations: Rainbow Babies & Children's Hospital (US)
Corresponding author: Baley, Jill E.
ORCID: Jacobs, Michael R.
Venue: The Journal of Pediatrics
Publisher: Elsevier BV
Published: 1990-05
Volume: 116
Issue: 5
Pages: 791-797
ISSN: 0022-3476 (ISSN-L)
DOI: 10.1016/s0022-3476(05)82674-5
OpenAlex: W2019367173
Cited by: 184
References: 25
Citations by year: 2026: 1 · 2025: 2 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 8 · 2019: 3 · 2018: 5 · 2017: 4 · 2016: 3 · 2015: 8 · 2014: 12 · 2013: 12 · 2012: 8
FWCI: 2.16
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: The Journal of Pediatrics (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
Health Sciences › Medicine › Infectious Diseases › Fungal Infections and Studies
Keywords: amphotericin B, 5-fluorocytosine, neonates, pharmacokinetics, serum drug concentration, cerebrospinal fluid drug concentration, interindividual variability, drug elimination, renal function, low birth weight infants, antifungal therapy, dosing interval, therapeutic drug monitoring
MeSH terms: Amphotericin B, Candidiasis, Flucytosine, Gestational Age, Humans, Infant, Low Birth Weight, Infant, Newborn, Infant, Premature, Kidney, Mycoses, Prognosis

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

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