Single‐Dose Gabapentin Pharmacokinetics and Safety in Healthy Infants and Children

Abstract

Gabapentin (Neurontin®) is a gamma‐aminobutyric acid analogue indicated in adults for adjunctive treatment of partial seizures with or without secondary generalization. Two studies were conducted to determine the single‐dose pharmacokinetics of gabapentin in healthy subjects age 1 month to 12 years and to guide dose selection in safety and efficacy trials in pediatric patients. Forty‐eight subjects were given single oral doses of gabapentin (10 mg/kg) while fasting. Enrollment was homogeneously distributed throughout the age range. Plasma samples were drawn predose and then serially for 24 hours postdose. Single doses of gabapentin were well tolerated by healthy pediatric subjects. Plots of pharmacokinetic parameters versus age suggested significant differences between younger (1 month to < 5 years) and older (∞5 to 12 years) subjects. Mean area under the plasma concentration‐time curve from zero to infinity (AUC _(0‐∞)) was 25.6 μg•h/mL in younger subjects and 36.0 μg•h/mL in older subjects (p < 0.001). Corresponding mean peak plasma concentrations (C_max) were 3.74 and 4.52 μg/ml (p < 0.05). Oral clearance (normalized for body weight) was 7.40 and 4.41 mL/min/kg in younger subjects and older subjects, respectively (p < 0.001). It was concluded that children between 1 month and < 5 years of age require approximately 30% higher daily doses of gabapentin than those ≥ 5 to 12 years of age.