European Journal of Clinical Pharmacology

, Volume 75, Issue 10, pp 1405–1414 | Cite as

Evaluation of a non-parametric modelling for meropenem in critically ill patients using Monte Carlo simulation

  • Ana Isabel Idoate GrijalbaEmail author
  • Azucena Aldaz Pastor
  • Pierre Marquet
  • Jean-Baptiste Woillard
Pharmacokinetics and Disposition



In critically ill patients treated with meropenem, the proposed pharmacokinetics/pharmacodynamics (PK/PD) efficacy index is to keep the free drug concentration 4–5 times above the minimum inhibitory concentration (MIC) of the germ isolated, for 100% of the interval regimen. The objectives were to design a population pharmacokinetics model for meropenem in critically ill patients and to evaluate different dosage schemes that achieve the optimal PK/PD objectives.


This retrospective, observational, single-centre study included 80 critically ill patients (154 samples) treated with meropenem between May 2011 and December 2017. Patient data, concentrations, treatment and bacteriological variables were collected from electronic medical records. Total and free concentrations of meropenem were modelled in Pmetrics. Monte Carlo simulations were performed to assess the probability of achieving the PK/PD target for different dosage regimens. For patients with available data, the number of patients with a free concentration 4 times higher or lower than the observed MIC for the P. aeruginosa and E. coli was investigated.


A one-compartment model with first-order elimination adequately described serum total and free meropenem concentrations. The only variable that significantly influenced the elimination constant of meropenem was the creatinine clearance (CLcr) calculated using the CKD-EPI formula. The highest probability of achieving the pharmacodynamic objective was with 3-h infusion dosage regimens. Sixty percent and 89% of patients attained a free drug concentration 4 times above the MIC for P. aeruginosa and E. coli respectively.


This study proposed different dosing regimens depending on renal clearance strata and the MIC of the germ targeted.


Meropenem Population pharmacokinetics Pmetrics Probability of target attainment 



We are grateful to K. Poole for manuscript editing.

Funding information

The project was supported by FBCN (Fundación Bancaria Caja Navarra) through a “mobility grant for Ph.D. research studies” for Ana Isabel Idoate Grijalba.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Pharmacy departmentClinica Universidad de NavarraPamplonaSpain
  2. 2.IPPRITTUniv. LimogesLimogesFrance
  3. 3.IPPRITTINSERMLimogesFrance
  4. 4.CHU LimogesLimogesFrance

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