Related Experiment Video
Updated: Feb 1, 2026
An In Vitro Bladder Model of Catheter-Associated Urinary Tract Infection
Published on: June 24, 2025
Physiologically-Based Pharmacokinetic model for Ciprofloxacin in children with complicated Urinary Tract Infection
Violeta Balbas-Martinez1, Robin Michelet2, Andrea N Edginton3
1Pharmacometrics and Systems Pharmacology, Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain; Ghent University, Faculty of Pharmaceutical Sciences, Laboratory of Medical Biochemistry and Clinical Analysis, Ghent, Belgium.
Insights
A physiologically-based pharmacokinetic (PBPK) model for ciprofloxacin in children with complicated urinary tract infections (cUTI) was developed. This model helps predict drug exposure and understand pharmacokinetic differences in cUTI patients.
Area of Science:
- Pharmacology
- Pediatric Medicine
- Computational Biology
Background:
- Population pharmacokinetic studies reveal significant differences in ciprofloxacin distribution and clearance in children with complicated urinary tract infections (cUTI) compared to healthy children.
- Understanding these pharmacokinetic variations is crucial for optimizing drug therapy in pediatric cUTI cases.
Purpose of the Study:
- To develop and evaluate a physiologically-based pharmacokinetic (PBPK) model for ciprofloxacin in pediatric patients with cUTI.
- To investigate the impact of renal impairment on ciprofloxacin pharmacokinetics in this population.
- To capture age-related pharmacokinetic changes and disease-specific alterations.
Main Methods:
- Developed an initial PBPK model in adults, incorporating age-dependent functions and validating with healthy pediatric data.
- Adapted the PBPK model for cUTI children by adjusting renal clearance (CL_Renal) and CYP1A2 clearance (CL_CYP1A2) based on renal function (KF).
- Evaluated the model using serum and urine samples from 22 cUTI children and performed parameter sensitivity analysis.
Main Results:
- The PBPK model successfully predicted ciprofloxacin exposure in both adults and children, accounting for age-related pharmacokinetic changes.
- Incorporating KF-dependent adjustments for CL_Renal and CL_CYP1A2 improved the prediction accuracy for plasma concentrations and fraction excreted unchanged in urine (fe) in pediatric cUTI patients.
- Parameter sensitivity analysis identified key influential parameters affecting volume of distribution (V) and total plasma clearance (CL).
Conclusions:
- The developed PBPK model is adequate for simulating ciprofloxacin dosing scenarios and predicting pharmacokinetic profiles in healthy children from 3 months of age onwards.
- Adjusting renal and CYP1A2 clearance by renal function (KF) partially explains pharmacokinetic differences observed in cUTI pediatric patients compared to healthy children.
- Further research into disease-specific alterations in cUTI is necessary to enhance the predictive accuracy of the PBPK model.
Abstract:
In a recent multicenter population pharmacokinetic study of ciprofloxacin administered to children suffering from complicated urinary tract infection (cUTI), the apparent volume of distribution (V) and total plasma clearance (CL) were decreased by 83.6% and 41.5% respectively, compared to healthy children. To understand these differences, a physiologically-based pharmacokinetic model (PBPK) for ciprofloxacin was developed for cUTI children. First, a PBPK model in adults was developed, modified incorporating age-dependent functions and evaluated with paediatric data generated from a published model in healthy children. Then, the model was then adapted to a cUTI paediatric population according to the degree of renal impairment (KF) affecting renal clearance (CLRenal,) and CYP1A2 clearance (CLCYP1A2). Serum and urine samples obtained from 22 cUTI children were used for model evaluation. Lastly, a parameter sensitivity analysis identified the most influential parameters on V and CL. The PBPK model predicted the ciprofloxacin exposure in adults and children, capturing age-related pharmacokinetic changes. Plasma concentrations and fraction excreted unchanged in urine (fe) predictions improved in paediatric cUTI patients once CLrenal and CLCYP1A2 were corrected by KF. The presented PBPK model for ciprofloxacin demonstrates its adequacy to simulate different dosing scenarios to obtain PK predictions in a healthy population from 3 months old onwards. Model adaptation of CLRenal and CLCYP1A2 according to KF explained partially the differences seen in the plasma drug concentrations and fe vs time profiles between healthy and cUTI children. Nevertheless, it is necessary to further investigate the disease-related changes in cUTI to improve model predictions.
Related Concept Videos
01:26Urinary Tract Infection I: Introduction
01:25Urinary Tract Infection II: Pathophysiology
01:17Urinary Tract Infection IV: Nursing Management
01:15Model Approaches for Pharmacokinetic Data: Physiological Models
01:30Urinary Tract Infection III: Diagnostic Studies and Interprofessional Care
01:13Physiological Pharmacokinetic Models: Assumption with Protein Binding