Pooled Population Pharmacokinetic Analysis and Dose Recommendations for Ciprofloxacin in Intensive Care Unit Patients with Obesity
(2024) In Journal of Clinical Pharmacology- 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... (More)
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.
(Less)
- author
- van Rhee, Koen P. ; Brüggemann, Roger J.M. ; Roberts, Jason A. ; Sjövall, Fredrik LU ; van Hest, Reinier M. ; Elbers, Paul W.G. ; Abdulla, Alan ; van der Linden, Paul D. and Knibbe, Catherijne A.J.
- organization
- publishing date
- 2024
- type
- Contribution to journal
- publication status
- in press
- subject
- keywords
- ciprofloxacin, dosing, ICU patients, obesity, pharmacokinetics
- in
- Journal of Clinical Pharmacology
- publisher
- SAGE Publications
- external identifiers
-
- scopus:85192783636
- pmid:38736038
- ISSN
- 0091-2700
- DOI
- 10.1002/jcph.2450
- language
- English
- LU publication?
- yes
- id
- daf894fe-7ed0-46ec-ad9a-7178bab3c549
- date added to LUP
- 2024-05-30 15:03:49
- date last changed
- 2024-06-27 17:24:21
@article{daf894fe-7ed0-46ec-ad9a-7178bab3c549, abstract = {{<p>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/m<sup>2</sup>) 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 m<sup>2</sup> may require higher dosages for the treatment of pathogens with minimal inhibitory concentration ≥0.25 mg/L.</p>}}, author = {{van Rhee, Koen P. and Brüggemann, Roger J.M. and Roberts, Jason A. and Sjövall, Fredrik and van Hest, Reinier M. and Elbers, Paul W.G. and Abdulla, Alan and van der Linden, Paul D. and Knibbe, Catherijne A.J.}}, issn = {{0091-2700}}, keywords = {{ciprofloxacin; dosing; ICU patients; obesity; pharmacokinetics}}, language = {{eng}}, publisher = {{SAGE Publications}}, series = {{Journal of Clinical Pharmacology}}, title = {{Pooled Population Pharmacokinetic Analysis and Dose Recommendations for Ciprofloxacin in Intensive Care Unit Patients with Obesity}}, url = {{http://dx.doi.org/10.1002/jcph.2450}}, doi = {{10.1002/jcph.2450}}, year = {{2024}}, }