ArticleJournal of pharmacokinetics and pharmacodynamics2017
A whole-body physiologically based pharmacokinetic (WB-PBPK) model of ciprofloxacin: a step towards predicting bacterial killing at sites of infection.
Article in Journal of pharmacokinetics and pharmacodynamics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Physiologically-based pharmacokinetic model to predict loading dose polymyxin B exposure in critically ill patients with sepsis.Frontiers in pharmacology · 2026Article
- A Physiologically Based Pharmacokinetic Model for the Prediction of Plasma and Bone Tissue Exposure after Prophylactic Administration of Ampicillin/Sulbactam in Patients with Osteonecrosis of the Jaw.Clinical pharmacokinetics · 2025Article
- A Comprehensive Physiologically Based Pharmacokinetic Framework of Ofloxacin: Predicting Disposition in Renal Impairment.Pharmaceutics · 2025Article
- PK/PD-Guided Strategies for Appropriate Antibiotic Use in the Era of Antimicrobial Resistance.Antibiotics (Basel, Switzerland) · 2025Review
- Artificial Intelligence to Close the Gap between Pharmacokinetic/Pharmacodynamic Targets and Clinical Outcomes in Critically Ill Patients: A Narrative Review on Beta Lactams.Antibiotics (Basel, Switzerland) · 2024Review
- Meropenem pharmacokinetics in cerebrospinal fluid: comparing intermittent and continuous infusion strategies in critically ill patients-a prospective cohort study.Antimicrobial agents and chemotherapy · 2024Observational
- Quantifying combined effects of colistin and ciprofloxacin against Escherichia coli in an in silico pharmacokinetic-pharmacodynamic model.Scientific reports · 2024Article
- A physiologically based pharmacokinetic/pharmacodynamic model to determine dosage regimens and withdrawal intervals of aditoprim againstFrontiers in pharmacology · 2024Article
- All Roads Lead to Rome: Enhancing the Probability of Target Attainment with Different Pharmacokinetic/Pharmacodynamic Modelling Approaches.Antibiotics (Basel, Switzerland) · 2023Review
- Key Factors in Effective Patient-Tailored Dosing of Fluoroquinolones in Urological Infections: Interindividual Pharmacokinetic and Pharmacodynamic Variability.Antibiotics (Basel, Switzerland) · 2022Review
- Optimization and Validation of Dosage Regimen for Ceftiofur againstInternational journal of molecular sciences · 2022Article
- Application of Semi-Mechanistic Pharmacokinetic and Pharmacodynamic Model in Antimicrobial Resistance.Pharmaceutics · 2022Review
- Predicting Antimicrobial Activity at the Target Site: Pharmacokinetic/Pharmacodynamic Indices versus Time-Kill Approaches.Antibiotics (Basel, Switzerland) · 2021Review
- Prediction of Human Pharmacokinetic Profiles of the Antituberculosis Drug Delamanid from Nonclinical Data: Potential Therapeutic Value against Extrapulmonary Tuberculosis.Antimicrobial agents and chemotherapy · 2021Article
- Prior information for population pharmacokinetic and pharmacokinetic/pharmacodynamic analysis: overview and guidance with a focus on the NONMEM PRIOR subroutine.Journal of pharmacokinetics and pharmacodynamics · 2020Review
- Physiologically Based Population Pharmacokinetic Modeling Approach for Ciprofloxacin in Bone of Patients Undergoing Orthopedic Surgery.ACS pharmacology & translational science · 2020Article
- Development and Application of a Water Temperature Related Physiologically Based Pharmacokinetic Model for Enrofloxacin and Its Metabolite Ciprofloxacin in Rainbow Trout.Frontiers in veterinary science · 2020Article
- Towards a Generic Tool for Prediction of Meropenem Systemic and Infection-Site Exposure: A Physiologically Based Pharmacokinetic Model for Adult Patients with Pneumonia.Drugs in R&D · 2019Article
- A Physiologically-Based Pharmacokinetic Model to Describe Ciprofloxacin Pharmacokinetics Over the Entire Span of Life.Clinical pharmacokinetics · 2018Review
- The use of PBPK modeling across the pediatric age range using propofol as a case.Journal of pharmacokinetics and pharmacodynamics · 2018Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The purpose of this study was to develop a whole-body physiologically based pharmacokinetic (WB-PBPK) model for ciprofloxacin for ICU patients, based on only plasma concentration data. In a next step, tissue and organ concentration time profiles in patients were predicted using the developed model. The WB-PBPK model was built using a non-linear mixed effects approach based on data from 102 adult intensive care unit patients. Tissue to plasma distribution coefficients (Kp) were available from the literature and used as informative priors. The developed WB-PBPK model successfully characterized both the typical trends and variability of the available ciprofloxacin plasma concentration data. The WB-PBPK model was thereafter combined with a pharmacokinetic-pharmacodynamic (PKPD) model, developed based on in vitro time-kill data of ciprofloxacin and Escherichia coli to illustrate the potential of this type of approach to predict the time-course of bacterial killing at different sites of infection. The predicted unbound concentration-time profile in extracellular tissue was driving the bacterial killing in the PKPD model and the rate and extent of take-over of mutant bacteria in different tissues were explored. The bacterial killing was predicted to be most efficient in lung and kidney, which correspond well to ciprofloxacin's indications pneumonia and urinary tract infections. Furthermore, a function based on available information on bacterial killing by the immune system in vivo was incorporated. This work demonstrates the development and application of a WB-PBPK-PD model to compare killing of bacteria with different antibiotic susceptibility, of value for drug development and the optimal use of antibiotics .
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