AI Article Synopsis
- The study aimed to create a porcine model to examine how moxifloxacin behaves in the central nervous system (CNS), particularly in brain extracellular fluid (ECF) and cerebrospinal fluid (CSF), after administering a single intravenous dose to pigs.
- Results showed that moxifloxacin concentrations in brain ECF were significantly lower than in plasma and lumbar CSF, suggesting ineffective penetration into the CNS for treating TB.
- Overall, the findings indicate that a single intravenous dose of moxifloxacin does not reach the necessary drug concentrations in the brain to effectively target TB, raising concerns for treatment in similar human cases.
Article 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.
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| http://dx.doi.org/10.1093/jac/dkae098 | DOI Listing |
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