Population pharmacokinetics of gabapentin in infants and children.

Abstract:

PURPOSE: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.

journal_name

Epilepsy Res

journal_title

Epilepsy research

authors

Ouellet D,Bockbrader HN,Wesche DL,Shapiro DY,Garofalo E

doi

10.1016/s0920-1211(01)00311-4

subject

Has Abstract

pub_date

2001-12-01 00:00:00

pages

229-41

issue

3

eissn

0920-1211

issn

1872-6844

pii

S0920121101003114

journal_volume

47

pub_type

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