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 (> 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.

Gabapentin for Management of Recurrent Pain in 22 Nonverbal Children with Severe Neurological Impairment: A Retrospective Analysis

“…[1][2][3] Gabapentin was used in this cohort given its safety and reported use in children with SNI. [6][7][8] The purpose of this retrospective analysis is to better understand gabapentin use in a larger cohort of individuals with SNI and recurrent pain behaviors.…”

Relation between vitamins of the b complex, GABA and glutamate, and their role in neurocognitive disorders -Brief review

“…Still on its effects, GABA has also been linked to the effectiveness of cascade action processes. Consistent with this hypothesis, Yildiz et al (2014) have shown by magnetic resonance spectroscopy (MRS) that superior performance of cascade action was associated with increased striatal GABA concentrations [98]. Another point, the active transcutaneous stimulation of the vagus nerve (tVNS) which increases the concentration of GABA and norepinephrine (NE), improved functions of response selection during the cascade action, compared with the stimulus simulation [99].…”

“…These results suggest a critical role of GABA in the neuromodulation of cascade action processes. They also suggest that the increase [98,99] not too high [100] of GABA levels are associated with better performance of these cascade actions. In another study, Steenbergen et al (2015b) aimed to provide converged and direct evidence about the possible key role of the GABAergic system in modulating the efficacy of cascade action [101].…”

Use of Second-Generation Antiepileptic Drugs in the Pediatric Population

“…However, gabapentin does not bind adjunct therapy in 247 pediatric patients with refractory partial to GABA receptors, mimic GABA, or affect GABA uptake. [84] seizures. [9] This study had a 6-week baseline period with a Currently, more is being discovered about the mechanism of 12-week double-blind phase.…”