ArticleAntimicrobial agents and chemotherapy2014
Population pharmacokinetic modeling of the unbound levofloxacin concentrations in rat plasma and prostate tissue measured by microdialysis.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Targeted Prostatic Delivery of Levofloxacin via a Novel Vas-Deferens Injection Device: A Pharmacokinetic Study in Rats.Pharmaceutics · 2026Article
- Antibiotic Pharmacokinetics and Prostate Penetration in Bacterial Prostatitis: A Systematic Review.Infectious diseases and therapy · 2026Review
- Unbound and Periprostatic Adipose Tissue Cefazolin Pharmacokinetics in Robotic-Assisted Radical Prostatectomy.Antibiotics (Basel, Switzerland) · 2026Article
- Translational Model to Predict Lung and Prostate Distribution of Levofloxacin in Humans.Pharmaceutics · 2026Article
- Bioanalytical considerations for quantification of ondansetron in rat microdialysis study using LC-MS/MS.Microchemical journal : devoted to the application of microtechniques in all branches of science · 2025Article
- Pharmacokinetics of Levofloxacin Entrapped in Non-Ionic Surfactant Vesicles (Niosomes) in Sprague Dawley Rats.Pharmaceutics · 2025Article
- Amphotericin B tissue penetration and pharmacokinetics in healthy andFrontiers in pharmacology · 2024Article
- Multiple drug transporters contribute to the brain transfer of levofloxacin.CNS neuroscience & therapeutics · 2023Article
- Article
- Efficacy of Human Exposures of Gepotidacin (GSK2140944) againstAntimicrobial agents and chemotherapy · 2019Article
- Interaction Between Sex and Organic Anion-Transporting Polypeptide 1b2 on the Pharmacokinetics of Regorafenib and Its Metabolites Regorafenib-N-Oxide and Regorafenib-Glucuronide in Mice.Clinical and translational science · 2019Article
- Reducing Antibacterial Development Risk for GSK1322322 by Exploring Potential Human Dose Regimens in Nonclinical Efficacy Studies Using Immunocompetent Rats.Antimicrobial agents and chemotherapy · 2017Article
- 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
- A Review on Microdialysis Calibration Methods: the Theory and Current Related Efforts.Molecular neurobiology · 2017Review
- Influence of Experimental Cryptococcal Meningitis in Wistar Rats on Voriconazole Brain Penetration Assessed by Microdialysis.Antimicrobial agents and chemotherapy · 2017Article
- Simultaneous Semimechanistic Population Analyses of Levofloxacin in Plasma, Lung, and Prostate To Describe the Influence of Efflux Transporters on Drug Distribution following Intravenous and Intratracheal Administration.Antimicrobial agents and chemotherapy · 2016Article
- Population pharmacokinetic modeling of cefadroxil renal transport in wild-type and Pept2 knockout mice.Xenobiotica; the fate of foreign compounds in biological systems · 2016Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Levofloxacin is a broad-spectrum fluoroquinolone used in the treatment of both acute and chronic bacterial prostatitis. Currently, the treatment of bacterial prostatitis is still difficult, especially due to the poor distribution of many antimicrobials into the prostate, thus preventing the drug to reach effective interstitial concentrations at the infection site. Newer fluoroquinolones show a greater penetration into the prostate. In the present study, we compared the unbound levofloxacin prostate concentrations measured by microdialysis to those in plasma after a 7-mg/kg intravenous bolus dose to Wistar rats. Plasma and dialysate samples were analyzed using a validated high-pressure liquid chromatography-fluorescence method. Both noncompartmental analysis (NCA) and population-based compartmental modeling (NONMEM 6) were performed. Unbound prostate tissue concentrations represented 78% of unbound plasma levels over a period of 12 h by comparing the extent of exposure (unbound AUC0-∞) of 6.4 and 4.8 h·μg/ml in plasma and tissue, respectively. A three-compartment model with simultaneous passive diffusion and saturable distribution kinetics from the prostate to the central compartment gave the best results in terms of curve fitting, precision of parameter estimates, and model stability. The following parameter values were estimated by the population model: V1 (0.38 liter; where V1 represents the volume of the central compartment), CL (0.22 liter/h), k12 (2.27 h(-1)), k21 (1.44 h(-1)), k13 (0.69 h(-1)), Vmax (7.19 μg/h), kM (0.35 μg/ml), V3/fuprostate (0.05 liter; where fuprostate represents the fraction unbound in the prostate), and k31 (3.67 h(-1)). The interindividual variability values for V1, CL, Vmax, and kM were 21, 37, 42, and 76%, respectively. Our results suggest that levofloxacin is likely to be substrate for efflux transporters in the prostate.
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