Safety and pharmacokinetics of repeat-dose micafungin in young infants

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 (48h and 120 days of life) with suspected candidemia or invasive candidiasis. Infants of body weight 1,000 and 1,000g received 7 and 10mg/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 2,101g and 30 weeks, respectively; in the 10-mg/kg/day group, they were 688g 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 24h (AUC 0-24), 258.1 and 291.2νgh/ml; clearance at steady state adjusted for body weight, 0.45 and 0.57ml/min/kg; maximum plasma concentration, 23.3 and 24.9ν g/ml; and volume of distribution at steady state adjusted for body weight, 341.4 and 542.8ml/kg. No deaths or discontinuations from treatment occurred. These data suggest that micafungin dosages of 7 and 10mg/kg/day are well tolerated and provide exposure levels that have been shown (in animal models) to be adequate for central nervous system coverage. © 2009 American Society for Clinical Pharmacology and Therapeutics.