OBJECTIVE: To evaluate the pharmacokinetics of amantadine in children with 
impaired consciousness from acquired brain injury.
DESIGN: Randomized, double-blind, placebo-controlled, crossover study with 
sparse sampling for pharmacokinetics.
SETTING: Tertiary care pediatric hospital.
PARTICIPANTS: Children, ages 6-18 years, with impaired consciousness 5-10 weeks 
after acquired brain injury.
METHODS: Subjects received amantadine for 3 weeks. Subjects were randomized to 
placebo or amantadine 4 mg/kg/day for 7 days followed by 6 mg/kg/day for 14 
days. Crossover was after a 7-day washout period.
MAIN OUTCOME MEASURES: The Coma/Near-Coma Scale and Coma Recovery Scale-Revised 
were done 3 times per week to evaluate arousal and consciousness. Plasma 
concentrations of amantadine were determined for pharmacokinetic parameter 
estimation and evaluation of the exposure-response relationship. Adverse events 
were monitored.
RESULTS: Nine subjects met the final inclusion and exclusion criteria, 7 of whom 
agreed to participate. Five subjects completed both arms of the study. 
Amantadine total body clearance was 0.17 L/h/kg with a half-life of 13.9 hours. 
Higher exposure of amantadine (average concentration of amantadine during 6 
mg/kg/day > 1.5 mg/L) may be associated with better recovery of consciousness.
CONCLUSIONS: Amantadine was well-tolerated in children with acquired brain 
injury and demonstrates pharmacokinetics similar to those reported for healthy 
young adults. Based on the preliminary data, higher dosing may be considered in 
the setting of brain injury.