Population pharmacokinetics of gabapentin in infants and children.
OBJECTIVE
To characterize gabapentin pharmacokinetics in infants and children using a population approach and to identify important demographic and/or physiologic determinants of gabapentin disposition.


METHODS
Gabapentin was administered in single doses of 10 mg/kg (N=48 healthy subjects, age 1 month-12 years) or in multiple doses of 10-65 mg/kg per day (N=205 patients with epilepsy, age 2 months-13 years) at 08:00, 14:00, and 20:00. Serial concentration-time data from the healthy subjects were combined with sparse data obtained in patients and were modeled using NONMEM.


RESULTS
Gabapentin oral clearance (l/h) was directly related to creatinine clearance (ml/min) with a slope of 0.116. The slope of the relationship was 36% greater in blacks than in subjects of other races. When oral clearance was normalized for body weight, young children (<5 years) had higher and more variable values than older children. Volume of distribution was related to body weight and appeared to differ between subjects and patients. Intersubject variability was approximately 30% for oral clearance and volume of distribution and was larger for the absorption rate constant and lag time. Residual variability, a measure of intrasubject variability and measurement error, was smaller in subjects than in patients.


CONCLUSIONS
On a weight basis, 33% larger doses would be required in younger children (<5 years) to achieve the same exposure as older children.
Ouellet
D
D
Pfizer Global Research & Development (Ann Arbor Laboratories), 2800 Plymouth Road, Ann Arbor, MI 48105, USA. daniele.ouellet@pfizer.com
Bockbrader
H N
HN
Wesche
D L
DL
Shapiro
D Y
DY
Garofalo
E
E
D000085:Acetates / Q000493:pharmacokinetics*; D000293:Adolescent; D000588:Amines; D000927:Anticonvulsants / Q000493:pharmacokinetics*; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D000077206:Gabapentin; D006801:Humans; D007223:Infant; D008657:Metabolic Clearance Rate; D012016:Reference Values; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D003404:Creatinine