Journal of Shandong University (Health Sciences) ›› 2026, Vol. 64 ›› Issue (4): 83-91.doi: 10.6040/j.issn.1671-7554.0.2025.0098

• Clinical Medicine • Previous Articles    

Optimizing neonatal meropenem dosage regimens based on pharmacokinetic/pharmacodynamic models

WANG Cuicui1, ZHENG Fengjia2, ZHANG Yahui3, WANG Xiaokang4, YU Ruihua4, HAO Wei4   

  1. 1. Medical Affairs Department, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China;
    2. Shandong Provincial Center for Disease Control and Prevention, Jinan 250101, Shandong, China;
    3. Clinical Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China;
    4. Neonatology Department, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China
  • Published:2026-04-09

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Abstract: Objective To analyze the population pharmacokinetics/pharmacodynamics(PPK/PD)characteristics of meropenem in Chinese neonates and to optimize the dosing regimen for neonatal Meropenem therapy. Methods A total of 50 neonates with confirmed bacterial infections, who received intravenous meropenem treatment at the Affiliated Provincial Hospital of Shandong First Medical University between January 1, 2023, and June 30, 2024, were included in this study. Blood samples were collected following the standard clinical dosing regimen of meropenem. Plasma concentrations of meropenem were determined using high-performance liquid chromatography. Nonlinear mixed-effect modeling software NONMEM V7.4 was employed for population pharmacokinetic analysis of meropenem. Monte Carlo simulations were used to evaluate the probability of target attainment(PTA)under different dosage regimens. Results Population pharmacokinetic analysis revealed that the pharmacokinetic characteristics of meropenem were best described by a first-order elimination, one-compartment model. The typical population pharmacokinetic parameters were a clearance rate of 0.301 L/h and a distribution volume of 0.885 L. The most significant covariates affecting the metabolism of meropenem in neonates were current body weight, gestational age, and birth age. Pharmacodynamic analysis showed that for bacteria with a minimum inhibitory concentration(MIC)≤2 mg/L, the minimum effective dosing regimen was 15 mg/kg administered as a 1-hour intravenous infusion every 8 hours, with a PTA of 70.76%. For bacteria with an MIC of 4 mg/L, the minimum effective dosing regimens were 20 mg/kg as a 3-hour intravenous infusion, 25 mg/kg as a 2-hour intravenous infusion, and 30 mg/kg as a 1-hour intravenous infusion, all administered every 8 hours, with PTAs of 74.74%, 72.67%, and 70.76%, respectively. When the pathogen was a highly resistant strain with an MIC of 8 mg/L, the minimum effective dosing regimen was 35 mg/kg as a 3-hour intravenous infusion every 8 hours, with a PTA of 71.69%. For bacteria with an MIC of 16 mg/L, the PTA of each monotherapy regimen of meropenem was below 70%. Conclusion Treatment optimization of meropenem for neonates can be significantly informed by actual therapeutic drug monitoring data and PPK/PD analysis.

Key words: Meropenem, Population pharmacokinetics/pharmacodynamics, Neonates, Dose optimization

CLC Number: 

  • R722.13
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