Related Experiment Video
Updated: Jun 24, 2026
Broth Microdilution In Vitro Screening: An Easy and Fast Method to Detect New Antifungal Compounds
Published on: February 14, 2018
Pharmacokinetics of an elevated dosage of micafungin in premature neonates
P Brian Smith1, Thomas J Walsh, William Hope
1Department of Pediatrics and Duke Clinical Research Institute, Duke University, Durham, NC 27715, USA. brian.smith@duke.edu
Background:
Determining the safety and pharmacokinetics of antifungal agents in neonates is important. A previous single-dose pharmacokinetic study of micafungin in neonates demonstrated that doses of 0.75 to 3 mg/kg produced lower plasma micafungin concentrations than in older patients because of increased apparent plasma clearance of micafungin in neonates. The primary objective of this study was to assess the safety and pharmacokinetics of an increased (15 mg/kg/d) dose of micafungin.
Methods:
A repeated dose, open-label pharmacokinetic, and safety trial of intravenous micafungin in 12 preterm neonates >48 hours of life with suspected systemic infections. Neonates received 15 mg/kg/d of micafungin for 5 days. Blood samples were drawn relative to either the fourth or fifth dose. Systemic exposure was assessed by examination of the plasma area under the curve.
Results:
The median birth weight and gestational age of the neonates were 775 g and 27 weeks, respectively. No adverse events related to micafungin were detected. The mean area under the curve and clearance for the cohort was 437.5 microg'h/mL and 0.575 mL/min/kg, respectively. The calculated clearance and volume of distribution for neonates was greater than that observed in older children and adults.
Conclusions:
These data suggest that 15 mg/kg dosing in premature neonates corresponds to an exposure of approximately 5 mg/kg in adults. No adverse events related to micafungin were observed.
Insights
A higher dose of micafungin (15 mg/kg/d) was safe and effective in preterm neonates. This antifungal dosing strategy achieved therapeutic drug exposure, similar to adult levels, without adverse events.
Area of Science:
- Neonatal pharmacology
- Antifungal drug safety
- Pharmacokinetics in infants
Background:
- Assessing antifungal safety and pharmacokinetics in neonates is crucial.
- Previous studies showed lower micafungin concentrations in neonates due to higher clearance.
- An increased micafungin dose was investigated to achieve therapeutic levels.
Purpose of the Study:
- To evaluate the safety and pharmacokinetics of an increased micafungin dose (15 mg/kg/d) in preterm neonates.
- To determine if this higher dose achieves adequate systemic exposure.
- To identify any micafungin-related adverse events in this population.
Main Methods:
- An open-label, repeated-dose pharmacokinetic and safety trial was conducted.
- Twelve preterm neonates received intravenous micafungin at 15 mg/kg/d for five days.
- Plasma concentrations and systemic exposure (area under the curve) were assessed.
Main Results:
- No adverse events attributed to micafungin were observed in the neonates.
- The mean area under the curve was 437.5 microg*h/mL with a clearance of 0.575 mL/min/kg.
- Neonatal clearance and volume of distribution exceeded those in older children and adults.
Conclusions:
- The 15 mg/kg/d micafungin dose in preterm neonates resulted in drug exposure comparable to a 5 mg/kg dose in adults.
- Micafungin was well-tolerated in this study population.
- This dosing regimen supports potential therapeutic use of micafungin in neonates.
Related Concept Videos
01:26Pharmacokinetics in Pediatric Patients: Drug Excretion
01:17Pharmacokinetics in Pediatric Patients: Drug Distribution
01:23Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption
01:24Pharmacokinetics in Pediatric Patients: Drug Metabolism
01:15Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions
01:29Drug Dosing: Infants and Children