Population pharmacokinetics of gabapentin in infants and children
Population pharmacokinetics of gabapentin in infants and children
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DOI：
10.1016/s0920-1211(01)00311-4
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发表时间：
2001-12-01
影响因子：
2.2
通讯作者：
Garofalo, E
中科院分区：
文献类型：
--
作者：
Ouellet, D;Bockbrader, HN;Garofalo, E
目的：利用人口方法表征加巴喷丁在婴儿和儿童中的药代动力学，并确定加巴喷丁处置的重要人口统计学和/或生理学决定因素。方法：加巴喷丁在08:00、14:00和20:00分别单次给药10mg /kg （N = 48名健康受试者，年龄1个月- 12岁）或多次给药，每天10- 65mg /kg （N = 205名癫痫患者，年龄2个月- 13岁）。健康受试者的连续浓度-时间数据与患者的稀疏数据相结合，并使用NONMEM建模。结果：加巴喷丁口服清除率（l/h）与肌酐清除率（ml/min）直接相关，斜率为0.116。这种关系的斜率在黑人中比在其他种族中大16%。当口服清除率与体重归一化时，幼儿（< 5岁）比大一点的儿童有更高和更多的变量值。体积分布与体重有关，在受试者和患者之间似乎有所不同。口服清除率和分布体积的受试者间变异性约为30%，吸收率常数和滞后时间的受试者间变异性更大。残差可变性是一种测量受试者内部可变性和测量误差的方法，在受试者中比在患者中要小。结论：以体重为基础，年龄较小的儿童（< 5岁）需要比年龄较大的儿童多33%的剂量才能达到相同的暴露量。(C) 2001 Elsevier Science B.V.版权所有
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.