Establishment and application of physiological-based pharmacokinet-ic model of ertapenem in elderly patients with chronic kidney disease
10.12092/j.issn.1009-2501.2025.05.005
- VernacularTitle:厄他培南在老年肾功能不全患者中生理药动学模型的建立与应用
- Author:
Jie ZONG
1
;
Xuan HU
;
Guifang DOU
;
Zhiyun MENG
;
Xiaoxia ZHU
;
RuoLan GU
;
Zhuona WU
;
Jingli GUAN
;
Hui GAN
Author Information
1. 军事医学研究院,北京 100850
- Publication Type:Journal Article
- Keywords:
ertapenem;
pharmacokinetics;
physi-ological-based pharmacokinetic models;
elderly pa-tients with chronic kidney disease
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2025;30(5):622-630
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To establish a physiological-based pharmacokinetic(PBPK)model of ertapen-em in elderly patients with chronic kidney disease,and to analyze the pharmacokinetic/pharmacody-namic index f％ T＞MIC at different doses.METH-ODS:The physicochemical properties and pharma-cokinetic characteristics of ertapenem were collect-ed by reviewing the literature and databases,and a healthy adult model was established in PKSim? software,and then extrapolated to the PBPK model of the elderly.The clinical pharmacokinetic re-search data were used to optimize and validate the model,and the mean folding error(MFE)was used as the index to evaluate the prediction perfor-mance of the model.The final model was used to simulate the in vivo exposure of elderly patients with chronic kidney disease after administration,and the pharmacokinetic/pharmacodynamic index of commonly used clinical dosing regimens was an-alyzed,and the recommended dosing regimens were given.RESULTS:The MFE of the area under the curve(AUC0-t),peak concentration(Cmax)and peak time(Tmmax)predicted by the established PBPK model of ertapenem in adults were 0.92,0.79 and 1.02,respectively,and the predicted value of the optimized PBPK model of ertapenem in the elderly was also consistent with the observed value of 0.5＜MFE＜2 standards,all of which have good predictive performance.With f％ T＞MIC greater than 40％as the drug efficacy target,the minimum inhibitory concentration(MIC)is 0.5-1 μg/mL for sensitive bacteria,and elderly patients with chronic kidney disease can consider reducing the drug dose as ap-propriate.CONCLUSION:The PBPK model of ertap-enem in elderly patients with renal insufficiency has been successfully established,and the model has good prediction performance and provides a reference for clinical personalized medication in el-derly patients with renal insufficiency.
