A seven-day study of the pharmacokinetics of intravenous levetiracetam in neonates: marked changes in pharmacokinetics occur during the first week of life

摘要

Introduction:Levetiracetam (LEV) is increasingly used in the treatment of neonatal seizures. The aim of this study was to determine pharmacokinetics in neonates with seizures and to obtain preliminary safety and efficacy data.Methods:Eighteen term neonates with seizures persisting after 20mg/kg of phenobarbital received intravenous LEV for 1?wk. LEV was administered as a 20 or 40?mg/kg bolus followed by 5–10?mg/kg/d. Pharmacokinetic data were analyzed using a nonlinear mixed-effects population approach. Continuous electroencephalogram monitoring allowed preliminary assessment of the efficacy of LEV in this population.Results:LEV clearance (CL) increased from a mean of 0.7?ml/min/kg (SD 0.27?ml/min/kg) on day 1 to 1.33?ml/min/kg (SD 0.35?ml/min/kg) by day 7. Mean half-life was 18.5?h (SD 7.1?h) on day 1 of the study and decreased to 9.1?h (SD 2.0?h) by day 7. The mean volume of distribution was 1.01 l/kg (SD 0.13 l/kg). No study-related serious adverse events were observed.Discussion:CL of LEV in neonates was higher than expected on the basis of immature renal function in term infants and increased significantly during the first week of life. More frequent dosing of LEV is needed in term infants to maintain serum concentrations in the range seen in children and adults.