1. Continuous evaluation of single-dose moxifloxacin concentrations in brain extracellular fluid, cerebrospinal fluid, and plasma: a novel porcine model.
- Author
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Mariager T, Terkelsen JH, Bue M, Öbrink-Hansen K, Nau R, Bjarkam CR, Nielsen H, and Bodilsen J
- Subjects
- Animals, Swine, Female, Cerebrospinal Fluid chemistry, Cerebrospinal Fluid metabolism, Anti-Bacterial Agents pharmacokinetics, Anti-Bacterial Agents cerebrospinal fluid, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents blood, Plasma chemistry, Fluoroquinolones pharmacokinetics, Fluoroquinolones cerebrospinal fluid, Fluoroquinolones administration & dosage, Fluoroquinolones blood, Models, Animal, Chromatography, High Pressure Liquid, Administration, Intravenous, Mass Spectrometry, Microbial Sensitivity Tests, Moxifloxacin pharmacokinetics, Moxifloxacin administration & dosage, Extracellular Fluid chemistry, Extracellular Fluid metabolism, Brain metabolism, Microdialysis
- Abstract
Background: Knowledge regarding CNS pharmacokinetics of moxifloxacin is limited, with unknown consequences for patients with meningitis caused by bacteria resistant to beta-lactams or caused by TB., Objective: (i) To develop a novel porcine model for continuous investigation of moxifloxacin concentrations within brain extracellular fluid (ECF), CSF and plasma using microdialysis, and (ii) to compare these findings to the pharmacokinetic/pharmacodynamic (PK/PD) target against TB., Methods: Six female pigs received an intravenous single dose of moxifloxacin (6 mg/kg) similar to the current oral treatment against TB. Subsequently, moxifloxacin concentrations were determined by microdialysis within five compartments: brain ECF (cortical and subcortical) and CSF (ventricular, cisternal and lumbar) for the following 8 hours. Data were compared to simultaneously obtained plasma samples. Chemical analysis was performed by high pressure liquid chromatography with mass spectrometry. The applied PK/PD target was defined as a maximum drug concentration (Cmax):MIC ratio >8., Results: We present a novel porcine model for continuous in vivo CNS pharmacokinetics for moxifloxacin. Cmax and AUC0-8h within brain ECF were significantly lower compared to plasma and lumbar CSF, but insignificantly different compared to ventricular and cisternal CSF. Unbound Cmax:MIC ratio across all investigated compartments ranged from 1.9 to 4.3., Conclusion: A single dose of weight-adjusted moxifloxacin administered intravenously did not achieve adequate target site concentrations within the uninflamed porcine brain ECF and CSF to reach the applied TB CNS target., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
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