不同日龄新生儿阿米卡星的群体药动学研究

Population pharmacokinetics of amikacin in different groups of newborn infant

目的:研究日龄和胎龄对新生儿阿米卡星药动学的影响.方法:收集常规血药浓度监测中的39例新生儿130对阿米卡星血药浓度时间数据进行分析;根据Sheiner等提出的群体药动学思想,编制估计群体参数的程序,目标函数最小值以Motne Carlo算法求得.结果:早产儿和足月儿阿米卡星的群体药动学参数分别为Ke:0.152±0.026/h和0.245±0.075/h,C1:93±4 mL/(h@kg)和123±10 mL/(h@kg);1～7天足月儿、8～27天足月儿、1～7天早产儿和8～27天早产儿的阿米卡星群体药动学参数依次为Ke:0.217±0.068/h、0.352±0.006/h、0.137±0.021/h和0.172±0.002/h,Cl:125±14 mL/(h@kg)、150.8±0 4 mL/(h@kg)、88±4 mL/(h@kg)和98.9±0.3 mL/(h@kg).结论:日龄和胎龄对新生儿阿米卡星药动学有显著影响.

Aim:To construct a population pharmacokinetic model able to study amikacin pharmacokinetics in newborn infants. Methods: Data used in this study were obtained from 39 neonates with 130 serum samples.A one-compartment open model was used to describe the kinetics of amikacin after the intravenous infusion.Following Sheiner s idea of population pharmacokinetics,we made the programs to estimate population parameter of amikacin. The target function minimality was obtained from Monte Carlo algorithm. Results:For the premature and the term neonate,fitted population pharmacokinetic parameters ( mean ± standard deviation ) were as follows:Ke: 0. 152 ±0. 026/h and 0. 245 ± 0. 075 /h, Cl: 93 ± 4 mL/(h·kg) and 123±10 mL/(h·kg) . For 1 - 7 day old term neonate, 8 - 27 day old term neonate, 1-7 day old premature and 8-27 day old premature, Ke and Cl were 0.217 ±0. 068/h, 0. 351±0. 006/h,0. 137±0.021/h,0. 172 ±0. 002/h and 125±14 mL/(h·kg), 150. 8 ± 0. 4 mL/(h ·kg),88±4mL/(h·kg),98. 9±0. 3 mL/(h·kg), respectively. Conclusion:Both postnatal age and gestational age obviously affects the pharmacokinetics of amikacin in newborn infant.