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Meropenem population pharmacokinetics and model-based dosing optimisation in patients with serious bacterial infection
  1. Irena Murínová1,2,
  2. Martin Švidrnoch3,
  3. Tomáš Gucký3,
  4. David Řezáč4,
  5. Jan Hlaváč5,
  6. Ondřej Slanař5,
  7. Martin Šíma5
  1. 1 Department of Clinical Pharmacy, Military University Hospital Prague, Prague, Czech Republic
  2. 2 Department of Applied Pharmacy, Faculty of Pharmacy, Masaryk University, Brno, Czech Republic
  3. 3 Laboratory of Pharmacology and Toxicology, AGEL Laboratories, Nový Jičín, Czech Republic
  4. 4 Department of Infectious Diseases, First Faculty of Medicine, Charles University and Military University Hospital Prague, Prague, Czech Republic
  5. 5 Department of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
  1. Correspondence to Dr Martin Šíma, Department of Pharmacology, General University Hospital in Prague, Praha, Czech Republic; martin.sima{at}


Objectives The objective of this study was to develop a population pharmacokinetic model of meropenem in a heterogeneous population of patients with a serious bacterial infection in order to propose dosing optimisation leading to improved achievement of the pharmacokinetic/pharmacodynamic (PK/PD) target.

Methods A total of 174 meropenem serum levels obtained from 144 patients during therapeutic drug monitoring were analysed using a non-linear mixed-effects modelling approach and Monte Carlo simulation was then used to compare various dosing regimens in order to optimise PK/PD target attainment.

Results The meropenem volume of distribution of the patient population was 54.95 L, while clearance started at 3.27 L/hour and increased by 0.91 L/hour with each 1 mL/s/1.73 m2 of estimated glomerular filtration rate. Meropenem clearance was also 0.31 L/hour higher in postoperative patients with central nervous system infection. Meropenem administration by continuous infusion showed a significantly higher probability of attaining the PK/PD target than a standard 30 min infusion (95.3% vs 49.5%).

Conclusions A daily meropenem dose of 3 g, 6 g and 10.5 g administered by continuous infusion was shown to be accurate for patients with moderate to severe renal impairment, normal renal function to mild renal impairment and augmented renal clearance, respectively.

  • critical care
  • administration, intravenous
  • drug monitoring
  • pharmacy service, hospital
  • practice guideline

Data availability statement

Data are available upon reasonable request.

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