Determination of population pharmacokinetic parameters for amikacin in neonates using mixed-effect models
Determination of population pharmacokinetic parameters for amikacin in neonates using mixed-effect models
复制标题
DOI：
10.1007/s002280050389
复制
发表时间：
1998-01-01
影响因子：
2.9
通讯作者：
Adhikari, M
中科院分区：
文献类型：
--
作者：
Botha, JH;du Preez, M;Adhikari, M
目的：采用非线性混合效应模型（NONMEM）研究了丁胺卡那霉素在新生儿体内的群体药代动力学。方法：53例平均胎龄为35.1周、平均开始治疗日龄为3.1天的黑人新生儿，共获得106份丁胺卡那霉素稳态血药浓度。结果：清除率（CL）和分布容积（V）的最终模型为：CL（1.h（-1））= 0.031WT（1.45）× P和V（1）= 0.316WT（1.44）其中WT =出生体重（kg），P = 1.28（女孩）和1.0（男孩）。在模型中纳入其他固定效应参数并未显著改善数据拟合。CL和V的个体间变异性分别为18%和13%，个体内变异性为29%。CL、V和半衰期的平均值（95% CI）分别为0.048（0.045，0.051）l.h（-1）.kg（-1）、0.434（0.414，0.453）l.kg（-1）和6.4（6.2，6.6）h。结论：出生体重是CL和V的重要决定因素，在该数据集中，性别也被发现影响CL。平均群体药代动力学值在先前使用传统方法获得的其他新生儿群体的范围内。
Objective: The population pharmacokinetics of amikacin, in neonates, was investigated using the nonlinear mixed effects model (NONMEM),Methods: One hundred and six steady-state amikacin ser um levels were obtained from 53 black neonates with a mean gestational age of 35.1 weeks and mean age at the start of treatment of 3.1 days. A one-compartment model was used to fit the data.Results: The final models for clearance (CL) and volume of distribution (V) were:CL(l.h(-1)) = 0.031WT(1.45) x P and V(l) = 0.316WT(1.44)where WT = birth weight (kg) and P = 1.28 for girls and 1.0 for boys. Inclusion of other fixed effect parameters in the model did not significantly improve the fit of the data. The inter-individual variability for CL and V were 18% and 13%, respectively, Intra-individual variability was 29%. Mean (95% CI) values of CL, V and half-life were 0.048 (0.045, 0.051) l.h(-1).kg(-1), 0.434 (0.414, 0.453)l.kg(-1) and 6.4 (6.2, 6.6)h respectively. Conclusion: Birth weight was an important determinant of both CL and V and, in this data set, gender was also found to influence CL. Mean population pharmacokinetic values were within the range of those previously derived for other neonatal populations using traditional methods.