Debord J, Pessis C, Voultoury J C, Marquet P, Lotfi H, Merle L, Lachâtre G
Service de Pharmacologie-Toxicologie, Hôpital Dupuytren, Limoges, France.
Fundam Clin Pharmacol. 1995;9(1):57-61. doi: 10.1111/j.1472-8206.1995.tb00266.x.
The population pharmacokinetics of amikacin was studied in 40 intensive care unit patients (212 plasma concentrations) by NPEM algorithm using a one-compartment model. The population was best characterized by the following pharmacokinetic parameters: renal clearance relative to creatinine clearance (Cs = 0.96 +/- 0.33), and either the total volume of distribution (Vd = 23.9 +/- 7.0 l) or the volume of distribution relative to body weight (Vs = 0.36 +/- 0.10 l.kg-1. The volume of distribution was increased with respect to the usual value of 0.25 l.kg-1. The statistical distribution of these pharmacokinetic parameters was approximately gaussian, with no significant correlation between volume of distribution and clearance. The medians and standard deviations of Cs and Vs were used as reference population values to estimate the pharmacokinetics of amikacin in a second group of 29 patients by the bayesian method, with two blood samples per patient. For each patient, the fitted parameters were able to predict the plasma concentrations of amikacin during the next 72 h with no significant bias and good precision (2.9 mg.l-1 for peaks and 0.5 mg.l-1 for troughs). This study confirms the ability of the NPEM algorithm to provide reference population values for use in bayesian monitoring of aminoglycoside therapy.
采用一室模型，运用非线性混合效应模型（NPEM）算法，对40例重症监护病房患者（共212个血药浓度数据）的阿米卡星群体药代动力学进行了研究。该群体的最佳药代动力学参数特征如下：肾清除率与肌酐清除率的比值（Cs = 0.96±0.33），以及总体分布容积（Vd = 23.9±7.0 L）或分布容积与体重的比值（Vs = 0.36±0.10 L·kg⁻¹）。分布容积相对于通常值0.25 L·kg⁻¹有所增加。这些药代动力学参数的统计分布近似于高斯分布，分布容积与清除率之间无显著相关性。将Cs和Vs的中位数及标准差用作参考群体值，通过贝叶斯方法对第二组29例患者的阿米卡星药代动力学进行估计，每位患者采集两份血样。对于每位患者，拟合参数能够无显著偏差且高精度地预测接下来72小时内的阿米卡星血药浓度（峰浓度为2.9 mg·L⁻¹，谷浓度为0.5 mg·L⁻¹）。本研究证实了NPEM算法能够提供参考群体值，用于氨基糖苷类药物治疗的贝叶斯监测。
