Abstract：
The objective of this project is to compare the results of the same study carried out on NONMEM and nlmixr2. This analysis consists of evaluating previously published population pharmacokinetic models of gentamicin and tobramycin in our population of interest with sparse concentrations. A literature review was performed to determine the gentamicin and tobramycin models in critically ill adult patients. In parallel, gentamicin and tobramycin dosing data, information on the treatment, the patient, and the bacteria were collected retrospectively in 2 Quebec establishments. The external evaluations were previously performed using NONMEM Version 7.5. Model equations were rewritten with R, and external evaluations were performed using nlmixr2. Predictive performance was assessed based on the estimation of bias and imprecision of the prediction error for maximum a posteriori (MAP) Bayesian PK parameter and observed concentrations. Comparison between nlmixr2 and NONMEM was performed on 4 gentamicin and 3 tobramycin population pharmacokinetic models. Compared to NONMEM, for gentamicin and tobramycin clearance and central volume of distribution, nlmixr2 produced individual pharmacokinetic parameters with bias values ranging from -32.5% to 5.67% and imprecision values ranging from 6.33% to 32.5%. Despite these differences, population bias and imprecision for sparse concentrations were low and ranged from 0% to 5.3% and 0.2% to 6.5%, respectively. The external evaluations performed with both software packages resulted in the same interpretation in terms of population predictive performance for all 7 models. Nlmxir2 showed comparable predictive performance with NONMEM with sparse concentrations that are, at most, sampled twice within a single dose administration (peak and trough).
摘要：
该项目的目的是比较在NONMEM和nlmixr2上进行的相同研究的结果。该分析包括评估先前发表的庆大霉素和妥布霉素在我们感兴趣的人群中浓度稀疏的群体药代动力学模型。进行文献综述以确定危重成年患者的庆大霉素和妥布霉素模型。并行,庆大霉素和妥布霉素剂量数据，关于治疗的信息，病人,细菌是在魁北克的2个机构中回顾性收集的。外部评估以前使用NONMEM版本7.5进行。用R重写了模型方程，使用nlmixr2进行外部评估。基于对最大后验（MAP）贝叶斯PK参数和观察浓度的预测误差的偏差和不精确性的估计来评估预测性能。nlmixr2和NONMEM在4个庆大霉素和3个妥布霉素群体药代动力学模型上进行比较。与非MEM相比，庆大霉素和妥布霉素的清除率和中央分布量，nlmixr2产生的个体药代动力学参数的偏差值范围为-32.5％至5.67％，不精确值范围为6.33％至32.5％。尽管存在这些差异,稀疏浓度的人群偏倚和不精确程度较低，范围从0%到5.3%和0.2%到6.5%，分别。使用两个软件包进行的外部评估在所有7个模型的种群预测性能方面产生了相同的解释。Nlmxir2显示出与稀疏浓度的NONMEM相当的预测性能，最多,在单剂量给药（峰谷）内采样两次。
