Pooled Population Pharmacokinetic Analysis and Dose Recommendations for Ciprofloxacin in Intensive Care Unit Patients with Obesity

Author:

van Rhee Koen P.123ORCID,Brüggemann Roger J.M.45,Roberts Jason A.6789,Sjövall Fredrik1011,van Hest Reinier M.12,Elbers Paul W.G.13,Abdulla Alan14,van der Linden Paul D.1,Knibbe Catherijne A.J.315

Affiliation:

1. Department of Clinical Pharmacy Tergooi MC Hilversum The Netherlands

2. Department of Clinical Pharmacy St Jansdal Hospital Harderwijk The Netherlands

3. Division of Systems Biomedicine and Pharmacology Leiden Academic Centre for Drug Research Leiden The Netherlands

4. Department of Pharmacy and Radboud Institute of Health Science Radboud University Medical Center Nijmegen The Netherlands

5. Center for Infectious Diseases Radboud University Medical Center Nijmegen The Netherlands

6. University of Queensland, Centre for Clinical Research Faculty of Medicine The University of Queensland Brisbane Australia

7. Herston Infectious Diseases Institute (HeIDI) Metro North Health Brisbane Australia

8. Departments of Pharmacy and Intensive Care Medicine Royal Brisbane and Women's Hospital Brisbane Australia

9. Division of Anaesthesiology Critical Care Emergency and Pain Medicine Nîmes University Hospital, University of Montpellier Nîmes France

10. Department of Intensive Care and Perioperative Medicine Skane University Hospital Malmö Sweden

11. Mitochondrial Medicine Lund University Lund Sweden

12. Department of Pharmacy and Clinical Pharmacology Amsterdam UMC, University of Amsterdam Amsterdam The Netherlands

13. Department of Intensive Care Medicine Amsterdam UMC, Vrije Universiteit Amsterdam Amsterdam The Netherlands

14. Department of Hospital Pharmacy Erasmus University Medical Center Rotterdam The Netherlands

15. Department of Clinical Pharmacy St. Antonius Hospital Nieuwegein The Netherlands

Abstract

AbstractRecent studies have explored the influence of obesity and critical illness on ciprofloxacin pharmacokinetics. However, variation across the subpopulation of individuals with obesity admitted to the intensive care unit (ICU) with varying renal function remains unexamined. This study aims to characterize ciprofloxacin pharmacokinetics in ICU patients with obesity and provide dose recommendations for this special population. Individual patient data of 34 ICU patients with obesity (BMI >30 kg/m2) from four studies evaluating ciprofloxacin pharmacokinetics in ICU patients were pooled and combined with data from a study involving 10 individuals with obesity undergoing bariatric surgery. All samples were collected after intravenous administration. Non‐linear mixed effects modeling and simulation were used to develop a population pharmacokinetic model and describe ciprofloxacin exposure in plasma. Model‐based dose evaluations were performed using a pharmacokinetic/pharmacodynamic target of AUC/MIC >125. The data from patients with BMI ranging from 30.2 to 58.1 were best described by a two‐compartment model with first‐order elimination and a proportional error model. The inclusion of Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) as a covariate on clearance reduced inter‐individual variability from 57.3% to 38.5% (P < .001). Neither body weight nor ICU admission significantly influenced clearance or volume of distribution. Renal function is a viable predictor for ciprofloxacin clearance in ICU patients with obesity, while critical illness and body weight do not significantly alter clearance. As such, body weight and critical illness do not need to be accounted for when dosing ciprofloxacin in ICU patients with obesity. Individuals with CKD‐EPI >60 mL/min/1.73 m2 may require higher dosages for the treatment of pathogens with minimal inhibitory concentration ≥0.25 mg/L.

Publisher

Wiley

Reference22 articles.

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