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Continuous evaluation of single-dose moxifloxacin concentrations in brain extracellular fluid, cerebrospinal fluid, and plasma: a novel porcine model.
- Source :
-
Journal of Antimicrobial Chemotherapy (JAC) . Jun2024, Vol. 79 Issue 6, p1313-1319. 7p. - Publication Year :
- 2024
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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 (C max):MIC ratio >8. Results We present a novel porcine model for continuous in vivo CNS pharmacokinetics for moxifloxacin. C max 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 C max: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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03057453
- Volume :
- 79
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Journal of Antimicrobial Chemotherapy (JAC)
- Publication Type :
- Academic Journal
- Accession number :
- 177611548
- Full Text :
- https://doi.org/10.1093/jac/dkae098