ArticleEuropean journal of drug metabolism and pharmacokinetics2016
Prediction of the pharmacokinetics and tissue distribution of levofloxacin in humans based on an extrapolated PBPK model.
Article in European journal of drug metabolism and pharmacokinetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation Approaches: A Systematic Review of Published Models, Applications, and Model Verification.Drug metabolism and disposition: the biological fate of chemicals · 2015Pooled it
- Cost-effectiveness analysis of oral versus intravenous drip infusion of levofloxacin in the treatment of acute lower respiratory tract infection in Chinese elderly patients.Clinical interventions in aging · 2017Trial
- Multi-scale computational modeling towards efficacy in radiopharmaceutical therapies while minimizing side effects: Modeling of amino acid infusion.PLoS computational biology · 2025Article
- PK/PD-Guided Strategies for Appropriate Antibiotic Use in the Era of Antimicrobial Resistance.Antibiotics (Basel, Switzerland) · 2025Review
- Successful Treatment of Pyogenic Liver Abscess Caused byInfection and drug resistance · 2025Article
- Pharmacokinetic/Pharmacodynamic Evaluation of Aztreonam/Amoxicillin/Clavulanate Combination against New Delhi Metallo-β-Lactamase and Serine-β-Lactamase Co-ProducingPharmaceutics · 2023Article
- Migalastat Tissue Distribution: Extrapolation From Mice to Humans Using Pharmacokinetic Modeling and Comparison With Agalsidase Beta Tissue Distribution in Mice.Clinical pharmacology in drug development · 2021Article
- Computational Approaches in Preclinical Studies on Drug Discovery and Development.Frontiers in chemistry · 2020Review
- Population Pharmacokinetic Modeling as a Tool To Characterize the Decrease in Ciprofloxacin Free Interstitial Levels Caused by Pseudomonas aeruginosa Biofilm Lung Infection in Wistar Rats.Antimicrobial agents and chemotherapy · 2017Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study developed a physiologically based pharmacokinetic (PBPK) model in intraabdominally infected rats and extrapolated it to humans to predict the levofloxacin pharmacokinetics and penetration into tissues. Twelve male rats with intraabdominal infections induced by Escherichia coli received a single dose of 50 mg/kg body weight of levofloxacin. Blood plasma was collected at 5, 10, 20, 30, 60, 120, 240, 480 and 1440 min after injection, respectively. A PBPK model was developed in rats and extrapolated to humans using GastroPlus software. The predictions were assessed by comparing predictions and observations. In the plasma concentration-versus-time profile of levofloxacin in rats, C max was 23.570 μg/ml at 5 min after intravenous injection, and t1/2 was 2.38 h. The plasma concentration and kinetics in humans were predicted and validated by the observed data. Levofloxacin penetrated and accumulated with high concentrations in the heart, liver, kidney, spleen, muscle and skin tissues in humans. The predicted tissue-to-plasma concentration ratios in abdominal viscera were between 1.9 and 2.3. When rat plasma concentrations were known, extrapolation of a PBPK model was a method to predict the drug pharmacokinetics and penetration in humans. Levofloxacin had good penetration into the liver, kidney and spleen as well as other tissues in humans. This pathological model extrapolation may provide a reference for the study of antiinfective PK/PD. In our study, levofloxacin penetrated well into abdominal organs. Also ADR monitoring should be implemented when using levofloxacin.
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