Pooled Population Pharmacokinetic Analysis and Dose Recommendations for Ciprofloxacin in Intensive Care Unit Patients with Obesity
The Journal of Clinical Pharmacology, vol. 64, pp. 1165–1172
Abstract
Abstract Recent 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.
Authors 9
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Koen P. van Rhee corresponding Aachen Division of Systems Biomedicine and Pharmacology Leiden Academic Centre for Drug Research Leiden The Netherlands Division of Systems Biomedicine and Pharmacology Leiden Academic Centre for Drug Research
Affiliation as printed
Department of Clinical Pharmacy St Jansdal Hospital Harderwijk The Netherlands
Department of Clinical Pharmacy Tergooi MC Hilversum The Netherlands
Division of Systems Biomedicine and Pharmacology Leiden Academic Centre for Drug Research Leiden The Netherlands
Department of Clinical Pharmacy, St Jansdal Hospital, Harderwijk, The Netherlands
Department of Clinical Pharmacy, Tergooi MC, Hilversum, The Netherlands
Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden, The Netherlands
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Radboud University Nijmegen · Radboud University Medical Center · Radboud Institute for Health Sciences
Affiliation as printed
Center for Infectious Diseases Radboud University Medical Center Nijmegen The Netherlands
Department of Pharmacy and Radboud Institute of Health Science Radboud University Medical Center Nijmegen The Netherlands
Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
Department of Pharmacy and Radboud Institute of Health Science, Radboud University Medical Center, Nijmegen, The Netherlands
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The University of Queensland · Université de Montpellier · Royal Brisbane and Women's Hospital · Metro North Hospital and Health Service
Affiliation as printed
Departments of Pharmacy and Intensive Care Medicine Royal Brisbane and Women's Hospital Brisbane Australia
Division of Anaesthesiology Critical Care Emergency and Pain Medicine Nîmes University Hospital, University of Montpellier Nîmes France
Herston Infectious Diseases Institute (HeIDI) Metro North Health Brisbane Australia
University of Queensland, Centre for Clinical Research Faculty of Medicine The University of Queensland Brisbane Australia
Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia
Herston Infectious Diseases Institute (HeIDI), Metro North Health, Brisbane, Australia
University of Queensland, Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia
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Lund University · Skåne University Hospital
Affiliation as printed
Department of Intensive Care and Perioperative Medicine Skane University Hospital Malmö Sweden
Mitochondrial Medicine Lund University Lund Sweden
Department of Intensive Care and Perioperative Medicine Skane University Hospital Malmö Sweden
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Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Pharmacy and Clinical Pharmacology Amsterdam UMC, University of Amsterdam Amsterdam The Netherlands
Department of Pharmacy and Clinical Pharmacology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
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Amsterdam University Medical Centers · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Intensive Care Medicine Amsterdam UMC, Vrije Universiteit Amsterdam Amsterdam The Netherlands
Department of Intensive Care Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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Affiliation as printed
Department of Hospital Pharmacy Erasmus University Medical Center Rotterdam The Netherlands
Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands
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Affiliation as printed
Department of Clinical Pharmacy Tergooi MC Hilversum The Netherlands
Department of Clinical Pharmacy, Tergooi MC, Hilversum, The Netherlands
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Catherijne A. J. Knibbe Aachen Division of Systems Biomedicine and Pharmacology Leiden Academic Centre for Drug Research Leiden The Netherlands Division of Systems Biomedicine and Pharmacology Leiden Academic Centre for Drug Research
Leiden University · St. Antonius Ziekenhuis
Affiliation as printed
Department of Clinical Pharmacy St. Antonius Hospital Nieuwegein The Netherlands
Division of Systems Biomedicine and Pharmacology Leiden Academic Centre for Drug Research Leiden The Netherlands
Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands
Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden, The Netherlands
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