Population pharmacokinetics of meropenem in critically ill children with different renal functions

Eur J Clin Pharmacol. 2020 Jan;76(1):61-71. doi: 10.1007/s00228-019-02761-7. Epub 2019 Oct 26.


Purpose: We aimed to develop a meropenem population pharmacokinetic (PK) model in critically ill children and simulate dosing regimens in order to optimize patient exposure.

Methods: Meropenem plasma concentration was quantified by high-performance liquid chromatography. Meropenem PK was investigated using a non-linear mixed-effect modeling approach.

Results: Forty patients with an age of 16.8 (1.4-187.2) months, weight of 9.1 (3.8-59) kg, and estimated glomerular filtration rate (eGFR) of 151 (19-440) mL/min/1.73 m2 were included. Eleven patients received continuous replacement renal therapy (CRRT). Concentration-time courses were best described by a two-compartment model with first-order elimination. Body weight (BW), eGFR, and CRRT were covariates explaining the between-subject variabilities on central/peripheral volume of distribution (V1/V2), inter-compartment clearance (Q), and clearance (CL): V1i = V1pop × (BW/70)1, Qi = Qpop × (BW/70)0.75, V2i = V2pop × (BW/70)1, CLi = (CLpop × (BW/70)0.75) × (eGFR/100)0.378) for patients without CRRT and CLi = (CLpop × (BW/70)0.75) × 0.9 for patients with CRRT, where CLpop, V1pop, Qpop, and V2pop are 6.82 L/h, 40.6 L, 1 L/h, and 9.2 L respectively normalized to a 70-kg subject. Continuous infusion, 60 and 120 mg/kg per day, is the most adequate dosing regimen to attain the target of 50% fT > MIC and 100% fT > MIC for patients infected by bacteria with high minimum inhibitory concentration (MIC) value (> 4 mg/L) without risk of accumulation except in children with severe renal failure.

Conclusion: Continuous infusion allows reaching the fT > MIC targets safely in children with normal or increased renal clearance.

Keywords: Critically ill children; Meropenem; Pharmacokinetics.

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / therapeutic use
  • Child
  • Child, Preschool
  • Critical Illness
  • Dose-Response Relationship, Drug
  • Drug Dosage Calculations
  • Female
  • Humans
  • Infant
  • Infusions, Intravenous
  • Kidney / physiopathology
  • Kidney Function Tests
  • Male
  • Meropenem / blood
  • Meropenem / pharmacokinetics*
  • Meropenem / therapeutic use
  • Metabolic Clearance Rate
  • Renal Insufficiency


  • Anti-Bacterial Agents
  • Meropenem