John S Bradley1, David Benziger, Paula Bokesch, Richard Jacobs. 1. From the *Department of Pediatrics, Division of Infectious Diseases, University of California San Diego, School of Medicine, and Rady Children's Hospital, San Diego, CA; †Department of Clinical Research, Cubist Pharmaceuticals, Lexington, MA; and ‡Department of Pediatrics, University of Arkansas for Medical Sciences College of Medicine, University of Arkansas, Little Rock, AR.
Abstract
BACKGROUND: Daptomycin is approved for treatment of complicated skin/skin structure infections and Staphylococcus aureus bloodstream infections (bacteremia) in adults. This study was undertaken to determine the pharmacokinetics of daptomycin in pediatric patients 3-24 months of age with proven/suspected bacterial infection. METHODS: In this phase 1, multicenter, open-label, noncomparative pharmacokinetic and safety study, patients were enrolled in 3 age groups: 3-6, 7-12 and 13-24 months. Intravenous daptomycin (single dose) was infused over 30 minutes at 6 mg/kg in subjects 13-24 months of age and at 4 mg/kg in the younger groups. Blood was collected for analysis of daptomycin concentrations. RESULTS: Twenty-four subjects received daptomycin. Daptomycin exposures (area under the curve0-∞) in children 3-6 and 7-12 months of age receiving 4 mg/kg were similar (215 and 219 μg·h/mL, respectively). Children 13-24 months of age receiving a higher dose, 6 mg/kg, had higher exposures (282 μg·h/mL). Mean maximum plasma concentrations in the age groups were 38.7, 37.1 and 67.0 μg/mL, respectively. Daptomycin exposures based on mg/kg dosing were lower than previously reported for older children and adults, likely because of increased clearance and volume of distribution and decreased apparent elimination half-life. Single-dose daptomycin 4 and 6 mg/kg was well tolerated and was not associated with clinical or laboratory adverse events. CONCLUSIONS: To match known clinically and microbiologically effective exposures in adults, infants require higher mg/kg daptomycin doses. Daptomycin safety and efficacy have not been established in pediatric patients. Pediatric clinical trials are ongoing.
BACKGROUND:Daptomycin is approved for treatment of complicated skin/skin structure infections and Staphylococcus aureus bloodstream infections (bacteremia) in adults. This study was undertaken to determine the pharmacokinetics of daptomycin in pediatric patients 3-24 months of age with proven/suspected bacterial infection. METHODS: In this phase 1, multicenter, open-label, noncomparative pharmacokinetic and safety study, patients were enrolled in 3 age groups: 3-6, 7-12 and 13-24 months. Intravenous daptomycin (single dose) was infused over 30 minutes at 6 mg/kg in subjects 13-24 months of age and at 4 mg/kg in the younger groups. Blood was collected for analysis of daptomycin concentrations. RESULTS: Twenty-four subjects received daptomycin. Daptomycin exposures (area under the curve0-∞) in children 3-6 and 7-12 months of age receiving 4 mg/kg were similar (215 and 219 μg·h/mL, respectively). Children 13-24 months of age receiving a higher dose, 6 mg/kg, had higher exposures (282 μg·h/mL). Mean maximum plasma concentrations in the age groups were 38.7, 37.1 and 67.0 μg/mL, respectively. Daptomycin exposures based on mg/kg dosing were lower than previously reported for older children and adults, likely because of increased clearance and volume of distribution and decreased apparent elimination half-life. Single-dose daptomycin 4 and 6 mg/kg was well tolerated and was not associated with clinical or laboratory adverse events. CONCLUSIONS: To match known clinically and microbiologically effective exposures in adults, infants require higher mg/kg daptomycin doses. Daptomycin safety and efficacy have not been established in pediatric patients. Pediatric clinical trials are ongoing.
Authors: Miriam G Mooij; Anne T Nies; Catherijne A J Knibbe; Elke Schaeffeler; Dick Tibboel; Matthias Schwab; Saskia N de Wildt Journal: Clin Pharmacokinet Date: 2016-05 Impact factor: 6.447