Pharmacokinetics and adverse effects of amphotericin B in infants and children

Gideon Koren, Allan Lau, Julia Klein, Cheryl Golas, Monica Bologa-Campeanu, Steven Soldin, Stuart M. MacLeod, Charles Prober

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

The pharmacokinetics and safety of amphotericin B infusion were studied in 13 infants and children (age range 3 weeks to 18 years; median age 11 years) treated with the drug for proved (n=11) or suspected (n=2) fungal infections. The dose during the first day was 0.5 mg/kg, followed by a daily dose of 1 mg/kg for the rest of the treatment period in most patients. The drug was infused over 4 to 6 hours. During the first day, serum concentrations were above the target therapeutic level of 0.3 μg/ml in all patients at 2 and 6 hours from the start of the infusion, in 12 of 13 patients at 12 hours, but in only 6 of 13 patients at 24 hours. On the third day, all concentrations were >0.3 μg/ml throughout the 24-hour period, and in 12 of 13 patients were >0.5 μg/ml. The same kinetic profile prevalled on days 7 to 10 of therapy, with a tendency for increasing concentrations. Elimination half-life was 9.93±1.5 hours (mean±SEM), clearance rate 26±5 ml/kg · hr, and distribution volume 378±25 ml/kg. The half-life inversely correlated with patients' age. Pharmacokinetic values calculated during the first day were not different from those calculated on day 3. Significant decreases in hemoglobin, platelets, and serum potassium concentration were recorded along with significant increases in serum creatinine, urea, and aspartate transaminase values. Because of the large pharmacokinetic variability and the high rate of serious adverse effects, individualized dosing of amphotericin B based on therapeutic drug monitoring should be considered.

Original languageEnglish
Pages (from-to)559-563
Number of pages5
JournalJournal of Pediatrics
Volume113
Issue number3
DOIs
StatePublished - Sep 1988
Externally publishedYes

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