Population pharmacokinetics of gabapentin in infants and children
2001; Elsevier BV; Volume: 47; Issue: 3 Linguagem: Inglês
10.1016/s0920-1211(01)00311-4
ISSN1872-6844
AutoresDanièle Ouellet, Howard N. Bockbrader, David Wesche, Douglas Y. Shapiro, E Garofalo,
Tópico(s)Pharmaceutical studies and practices
ResumoPurpose: 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.
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