Population Pharmacokinetics and Dosing Simulations of Pentobarbital in the Pediatric Population

Pentobarbital is a barbiturate with sedative and anticonvulsant properties, occasionally used in pediatric patients for preoperative sedation, deep sedation during mechanical ventilation, and seizure control. Despite its long-standing clinical use, age-appropriate dosing remains challenging due to variability across studies and limited pediatric pharmacokinetic (PK) data. This study (NCT01431326) aimed to characterize the population pharmacokinetics of pentobarbital in pediatric patients (birth to 21 years) and evaluate dosing strategies using model-based simulations. A two-compartment population PK model, allometrically scaled to total body weight, adequately described pentobarbital plasma concentrations, with no additional covariates identified as significant. Simulations were conducted across four age groups: 1 to <2 years, 2 to <6 years, 6 to <12 years, and 12 to <18 years. Comparable exposures were achieved across groups, although older and heavier patients tended to exhibit slightly higher exposures when non-capped doses were applied. Based on simulation results, intravenous bolus doses of 1 mg/kg for preoperative sedation and 5 mg/kg followed by a continuous infusion of 1 mg/kg/h for seizure management appeared appropriate across the evaluated age range. For deep sedation, lower infusion rates (0.75 mg/kg/h) may be sufficient in older children (6 to 18 years) to match exposures observed in younger patients (1 to 6 years old) receiving 1 mg/kg/h. These findings support the currently recommended dosing regimens for pentobarbital in pediatric patients aged 1 to <18 years.