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Single-dose gabapentin pharmacokinetics and safety in healthy infants and children
G M Haig1, H N Bockbrader, D L Wesche
1Department of Clinical Pharmacology, Parke-Davis Pharmaceutical Research Division of Warner-Lambert Company, Ann Arbor, Michigan 48105, USA.
Insights
Pediatric patients aged 1 month to under 5 years require approximately 30% higher daily gabapentin doses than older children (5-12 years) due to pharmacokinetic differences. This finding aids pediatric gabapentin dosing.
Area of Science:
- Pharmacology
- Pediatric Medicine
- Clinical Pharmacy
Background:
- Gabapentin (Neurontin) is a gamma-aminobutyric acid analogue used for partial seizures in adults.
- Pediatric dosing requires understanding age-related pharmacokinetic variations.
- Previous studies focused on adult pharmacokinetics, necessitating pediatric-specific data.
Purpose of the Study:
- To determine single-dose gabapentin pharmacokinetics in healthy pediatric subjects aged 1 month to 12 years.
- To guide dose selection for pediatric safety and efficacy trials.
- To identify age-specific dosing recommendations for gabapentin in children.
Main Methods:
- Forty-eight healthy pediatric subjects (1 month to 12 years) received single oral gabapentin doses (10 mg/kg) under fasting conditions.
- Serial plasma samples were collected for 24 hours post-dose to analyze pharmacokinetic parameters.
- Subjects were grouped into younger (1 month to <5 years) and older (≥5 to 12 years) cohorts.
Main Results:
- Gabapentin was well tolerated in all pediatric subjects.
- Significant pharmacokinetic differences were observed between younger and older pediatric groups.
- Younger subjects exhibited lower area under the curve (AUC) and peak plasma concentration (Cmax) but higher normalized oral clearance compared to older subjects.
Conclusions:
- Children aged 1 month to <5 years require approximately 30% higher daily gabapentin doses than those aged 5 to 12 years.
- Age-dependent pharmacokinetic variability necessitates adjusted dosing strategies in pediatric populations.
- These findings support optimized gabapentin therapeutic regimens for 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 (> or =5 to 12 years) subjects. Mean area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) was 25.6 microg x h/mL in younger subjects and 36.0 microg x h/mL in older subjects (p < 0.001). Corresponding mean peak plasma concentrations (Cmax) were 3.74 and 4.52 microg/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 > or =5 to 12 years of age.