AIM: To establish a physiological-based pharmacokinetic (PBPK) model of ertapenem in elderly patients with chronic kidney disease, and to analyze the pharmacokinetic/pharmacodynamic index f%T>MIC at different doses. METHODS: The physicochemical properties and pharmacokinetic characteristics of ertapenem were collected 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 research data were used to optimize and validate the model, and the mean folding error (MFE) was used as the index to evaluate the prediction performance 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 analyzed, and the recommended dosing regimens were given. RESULTS: The MFE of the area under the curve (AUC0-t), peak concentration (Cmax) and peak time (Tmax) 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 appropriate. CONCLUSION: The PBPK model of ertapenem 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 elderly patients with renal insufficiency.