Population pharmacokinetics of gabapentin in infants and children

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 16% 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. (C) 2001 Elsevier Science B.V. All rights reserved.