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.
[1]Aalborg Univ Hosp, Dept Infect Dis, Aalborg, Denmark.
[2]Aalborg Univ Hosp, Dept Neurosurg, Aalborg, Denmark.
[3]Aarhus Univ Hosp, Dept Orthoped Surg, Aarhus, Denmark.
[4]Aarhus Univ Hosp, Aarhus Denmark Microdialysis Res Grp ADMIRE, Aarhus, Denmark.
[5]Godstrup Hosp, Dept Infect Dis, Internal Med, Herning, Denmark.
[6]Univ Med Ctr, Inst Neuropathol, Gottingen, Germany.
[7]Aalborg Univ, Dept Clin Med, Aalborg, Denmark.
(8.0+极速模式)