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Population pharmacokinetics of micafungin in pediatric patients and implications for antifungal dosing. Antimicrob Agents Chemother 2007 Oct;51(10):3714-9

Date

07/20/2007

Pubmed ID

17638696

Pubmed Central ID

PMC2043253

DOI

10.1128/AAC.00398-07

Scopus ID

2-s2.0-34948887165   89 Citations

Abstract

The echinocandins potentially have an important role in treatment of infections caused by Candida spp. and Aspergillus spp. in immunocompromised children. However, there are no population pharmacokinetic models of the echinocandins for pediatric patients. The safety and descriptive pharmacokinetics of micafungin in children were recently reported. However, a population pharmacokinetic model in children is needed in order to accurately determine the dosage of micafungin that produces an equivalent magnitude of drug exposure to that observed in adults. In order to explore the effect of weight on micafungin pharmacokinetics, a standard two-compartment pharmacokinetic model, a linear model, and an allometric power model were developed. For all three models, the fit to the data was excellent, with comparable measures of precision and bias. However, the superior log-likelihood value of the allometric power model suggested that it best reflected the data and was therefore chosen for a more detailed analysis of the magnitude and pattern of drug exposure which develop following the administration of micafungin. The allometric power model suggested that clearance in smaller children is higher than that predicted on the basis of weight alone. Consequently, a degree of dosage increase is required in smaller children to ensure comparable levels of drug exposure to those observed in larger children and adults. The allometric power model developed in this study enables identification of pediatric dosage regimens of micafungin which, based upon Monte Carlo simulations, result in equivalent drug exposures to those observed in adults, for which antifungal efficacy has been established.

Author List

Hope WW, Seibel NL, Schwartz CL, Arrieta A, Flynn P, Shad A, Albano E, Keirns JJ, Buell DN, Gumbo T, Drusano GL, Walsh TJ

Author

Cindy L. Schwartz MD, MPH Chief, Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adolescent
Algorithms
Antifungal Agents
Area Under Curve
Bayes Theorem
Child
Child, Preschool
Echinocandins
Female
Forecasting
Humans
Linear Models
Lipopeptides
Lipoproteins
Male
Models, Statistical
Monte Carlo Method
Population
jenkins-FCD Prod-461 7d7c6113fc1a2757d2947d29fae5861c878125ab