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Cited by 120Antifungal resistance and susceptibilityPharmaceutical studies and practicesAntibiotics Pharmacokinetics and Efficacy

Safety and pharmacokinetics of fluconazole in children with neoplastic diseases

Lee, James W., Seibel, Nita L., Amantea, Michael, Whitcomb, Patricia, Pizzo, Philip A., Walsh, Thomas J.·1992·The Journal of Pediatrics
DOI 10.1016/s0022-3476(05)81975-4
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Abstract

To evaluate the safety, tolerance, and pharmacokinetics of fluconazole in children with neoplastic diseases, we studied fluconazole in 26 children, aged 5 to 15 years, with normal renal function who were receiving treatment for cancer. The patients received fluconazole, 2, 4, or 8 mg/kg per day for 7 days intravenously for a 2-hour period. Patients had no nausea or vomiting related to fluconazole; three patients had an asymptomatic rise in hepatic aminotransferase values after four to six doses (one patient at 2 mg/kg per day and two patients at 8 mg/kg per day), which returned to normal within 2 weeks after discontinuation of the drug. Fluconazole showed linear first-order kinetics over the dosage range tested and during multiple dosing. After the first dose, mean clearance was 22.8 +/- 2.3 ml/min, volume of distribution 0.87 +/- 0.06 L/kg, and terminal elimination half-life 16.8 +/- 1.1 hours. Similarly, after the last dose, clearance was 19.4 +/- 1.3 ml/min, volume of distribution 0.84 +/- 0.04 L/kg, and terminal elimination half-life 18.1 +/- 1.2 hours. Patients receiving their first fluconazole dose of 8 mg/kg achieved peak serum levels of 9.5 +/- 0.4 microgram/ml and trough levels of 2.7 +/- 0.5 microgram/ml 24 hours later, and an area under the serum concentration-time curve from time zero to infinity of 186 +/- 16 micrograms.hr per milliliter. Renal clearance of fluconazole was 65% +/- 5% of total clearance and demonstrated the predominantly renal excretion of this drug. We suggest that the shorter serum half-life and the higher frequency of aminotransferase elevations in comparison with those of adults warrant careful investigation of fluconazole in controlled clinical trials.

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Crossref · 10.1016/s0022-3476(05)81975-4

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18 of 18 references verified0 citation errors · 0 not checkable

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  • Because of its more rapid clearance in children (plasma half-life, approximately 14 h), fluconazole at a dosage of 6 mg/kg q12h should be administered for treatment of life-threatening infections.

    “Because of its more rapid clearance in children (plasma halflife, ∼14 h) [89], fluconazole at a dosage of 6 mg/kg q12h should be administered for treatment of life-threatening infections.”

    From Guidelines for Treatment of Candidiasis (2004) · cites this paper as [89]

  • The pharmacokinetics of fluconazole vary with age.

    “The pharmacokinetics of fluconazole vary with age [89][90][91][92].”

    From Guidelines for Treatment of Candidiasis (2004) · cites this paper as [89]

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Authors
Lee, J. W., Seibel, N. L., Amantea, M., Whitcomb, P., Pizzo, P. A., & Walsh, T. J.
Affiliations
National Institutes of Health (US)
Corresponding author
Walsh, Thomas J.
ORCID
Venue
The Journal of Pediatrics
Publisher
Elsevier BV
Published
1992-06
Volume
120
Issue
6
Pages
987-993
ISSN
0022-3476 (ISSN-L)
DOI
10.1016/s0022-3476(05)81975-4
OpenAlex
W2068402403
Cited by
120
References
19
Citations by year
2026: 1 · 2025: 2 · 2021: 5 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 5 · 2014: 7 · 2013: 4 · 2012: 4
FWCI
5.69
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 › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
Keywords
fluconazole, pharmacokinetics, drug safety, childhood cancer, antifungal agents, renal clearance, elimination half-life, volume of distribution
MeSH terms
Child, Drug Administration Schedule, Drug Evaluation, Female, Humans, Kidney, Liver, Liver Function Tests, Male, Soft Tissue Neoplasms, Leukemia, Myeloid, Acute, Fluconazole, Precursor Cell Lymphoblastic Leukemia-Lymphoma

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