Pharmacokinetics and tolerability of single-dose daptomycin in young infants
Michael Cohen-Wolkowiez1, Kevin M Watt, Christoph P Hornik
1Department of Pediatrics, Duke University Medical Center, and †Duke Clinical Research Institute, Durham, NC 27715, USA.
Insights
Daptomycin (a key antibiotic) shows favorable pharmacokinetics and tolerability in infants under 120 days old. Infant daptomycin clearance is comparable to young children, suggesting appropriate dosing may be possible.
Area of Science:
- Pharmacology
- Neonatal Medicine
- Infectious Diseases
Background:
- Daptomycin is FDA-approved for specific infections, including complicated skin infections and Staphylococcus aureus bacteremia.
- Limited pharmacokinetic data exists for daptomycin in neonates and young infants.
Purpose of the Study:
- To characterize the single-dose pharmacokinetics of daptomycin in infants younger than 120 days.
- To assess the tolerability of daptomycin in this young infant population.
Main Methods:
- A single 6 mg/kg intravenous dose of daptomycin was administered to eligible infants (<120 days) with suspected systemic infections.
- An average of four post-dose plasma concentrations were measured per infant to determine pharmacokinetic parameters.
Main Results:
- Twenty infants were included, with median gestational age of 32 weeks and postnatal age of 3 days.
- Key pharmacokinetic parameters included a median 24-hour area under the curve of 262.4 mg×h/L, volume of distribution of 0.21 L/kg, total body clearance of 0.021 L/h/kg, and half-life of 6.2 hours.
- No adverse events were attributed to daptomycin, including normal creatine phosphokinase levels.
Conclusions:
- Daptomycin demonstrated predictable pharmacokinetics in young infants.
- Daptomycin clearance in this cohort was similar to children aged 2-6 years and higher than in older populations.
Background:
Daptomycin is approved for the treatment of complicated skin and skin-structure infections and Staphylococcus aureus bacteremia. We sought to characterize daptomycin single-dose pharmacokinetics and tolerability in young infants.
Methods:
Subjects < 120 days of age with suspected systemic infections were eligible for inclusion. Each subject was given a single 6 mg/kg intravenous dose of daptomycin. An average of 4 postdose concentrations per infant was obtained.
Results:
Data from 20 infants are presented. Median gestational age at birth and postnatal age were 32 weeks (range: 23, 40) and 3 days (1, 85), respectively. The median area under the concentration curve at 24 hours, volume of distribution, total body clearance and half-life of daptomycin were 262.4 mg×h/L (166.7, 340.2), 0.21 L/kg (0.11, 0.34), 0.021 L/h/kg (0.016, 0.034) and 6.2 hours (3.7, 9.0), respectively. No adverse events related to daptomycin were observed, including changes in creatine phosphokinase concentrations.
Conclusions:
Daptomycin clearance in young infants was similar to that in children 2-6 years of age and higher than that observed in adolescents and adults.
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