A Physiologically Based Pharmacokinetic Model of Ertapenem in Pediatric Patients With Renal Impairment
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Updated: Dec 17, 2025
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Published on: July 18, 2017
Lingling Ye1, Meng Ke1, Xiang You1
1Department of Pharmacy, The First Affiliated Hospital of Fujian Medical University, 20 Cha Zhong M. Rd, Fuzhou 350005, People's Republic of China.
Insights
This study developed a pharmacokinetic model to determine optimal ertapenem dosing for children with kidney impairment. The model accurately predicts drug exposure, ensuring effective treatment with adjusted doses for varying degrees of renal dysfunction.
Area of Science:
- Pharmacology and Therapeutics
- Pediatric Nephrology
- Mathematical Modeling in Medicine
Background:
- Ertapenem is a crucial antibiotic, but its use in pediatric patients with renal impairment requires better pharmacokinetic understanding.
- Existing pharmacokinetic data for ertapenem in children with kidney disease is limited, hindering optimal dosing strategies.
Purpose of the Study:
- To develop and validate a physiologically based pharmacokinetic (PBPK) model for ertapenem in pediatric patients with varying degrees of renal impairment.
- To predict ertapenem exposure and guide optimized dosing regimens in this vulnerable population.
Main Methods:
- A physiologically based pharmacokinetic (PBPK) model for ertapenem was established and validated using existing data from healthy individuals and adults with renal impairment.
- The validated PBPK model was used to simulate ertapenem disposition and predict drug exposure in pediatric patients across different stages of renal impairment.
- Pharmacodynamic targets, specifically %T > MIC (Time above Minimum Inhibitory Concentration), were evaluated using the PBPK model.
Main Results:
- The PBPK model demonstrated good predictive performance, with simulated results aligning closely with observed ertapenem data (fold error < 2).
- While Cmax (maximum concentration) remained similar, AUC (Area Under the Curve) significantly increased with worsening renal impairment in pediatric patients.
- Recommended ertapenem doses were adjusted downwards for mild, moderate, severe renal impairment, and end-stage renal disease to maintain therapeutic efficacy.
Conclusions:
- The developed PBPK model serves as a valuable tool for predicting ertapenem pharmacokinetics in pediatric patients with renal impairment.
- The model supports the generation of precise dosing recommendations, aiming for nearly 100% probability of achieving the target %T > MIC.
- Optimized ertapenem dosing strategies are crucial for effectively treating infections in children with kidney dysfunction.
Abstract:
Ertapenem is a widely used antibiotic; however, its pharmacokinetics has not been fully evaluated in children with renal impairment. A physiologically based pharmacokinetic (PBPK) model of ertapenem was established and validated to simulate its disposition in the healthy population and adults with renal impairment, as well as to predict the exposure in pediatric patients with renal impairment. The simulated PBPK modeling results and the observed data of ertapenem after intravenous administration of various regimens were consistent according to the fold error values of less than 2. Furthermore, %T > MIC of ertapenem was evaluated using the PBPK model. The Cmax was not significantly changed in pediatric patients with renal impairment compared to healthy children. However, the AUC was 1.42-fold, 1.84-fold, 2.37-fold, and 3.52-fold higher in mild, moderate, severe renal impairment, and end-stage renal disease, respectively, than that in healthy children and the doses of ertapenem were reduced to 13 mg/kg b.i.d, 9 mg/kg b.i.d, 6 mg/kg b.i.d, and 5 mg/kg b.i.d, respectively. The probability of achieving 40%T > MIC (MIC ≤ 4 μg/mL) was nearly 100% throughout the recommended dosing interval. In conclusion, our model can be used as a tool to generate better predictions for the most effective ertapenem dosing in pediatric patients.
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