Safety and pharmacokinetics of repeat-dose micafungin in young infants

Abstract

Given the risk of central nervous system infection, relatively high weight-based echinocandin dosages may be required for the successful treatment of invasive candidiasis and candidemia in young infants. This open-label study assessed the safety and pharmacokinetics (PK) of micafungin in 13 young infants (>48 h and <120 days of life) with suspected candidemia or invasive candidiasis. Infants of body weight > or =1,000 and <1,000 g received 7 and 10 mg/kg/day, respectively, for a minimum of 4-5 days. In the 7-mg/kg/day group, the mean baseline weight and gestational age were 2,101 g and 30 weeks, respectively; in the 10-mg/kg/day group, they were 688 g and 25 weeks, respectively. The median pharmacokinetic values for the 7- and 10-mg/kg/day groups, respectively, were as follows: area under the concentration-time curve from 0 to 24 h (AUC(0-24)), 258.1 and 291.2 microg x h/ml; clearance at steady state adjusted for body weight, 0.45 and 0.57 ml/min/kg; maximum plasma concentration, 23.3 and 24.9 micro g/ml; and volume of distribution at steady state adjusted for body weight, 341.4 and 542.8 ml/kg. No deaths or discontinuations from treatment occurred. These data suggest that micafungin dosages of 7 and 10 mg/kg/day are well tolerated and provide exposure levels that have been shown (in animal models) to be adequate for central nervous system coverage.

Conflict of interest statement

CONFLICT OF INTEREST

Authors declare the following potential conflicts of interest:

DK Benjamin Jr. receives support from the United States Government for his work in pediatric and neonatal clinical pharmacology (1R01HD057956-02, 1R01FD003519-01, 1U10-HD45962-06, 1K24HD058735-01, and Government Contract HHSN267200700051C), the non-profit organization Thrasher Research Foundation for his work in neonatal candidiasis (http://www.thrasherresearch.org), and from industry for neonatal and pediatric drug development (http://www.dcri.duke.edu/research/coi.jsp). Dr. PB Smith has received grant support from Astellas Pharma Global Development Inc. A Arrieta has received grant support and consultancy fees from Astellas Pharma Global Development Inc. PJ Sanchez has received grant support from Astellas Pharma Inc. LJ Arnold, LL Kovanda, T Sawamoto, and DN Buell are employees of Astellas Pharma Global Development Inc.

L Castro, WW Hope, TJ Walsh, and D Kaufman do not declare any potential conflicts of interest.

Figures

Figure 1

Individual plasma micafungin concentrations vs. time on day 4 of a repeated dosage regimen: 7 mg/kg/day in infants weighing ≥ 1,000 g (Panel A) and 10 mg/kg/day in infants weighing < 1,000 g (Panel B).