{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T14:56:47Z","timestamp":1774623407752,"version":"3.50.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T00:00:00Z","timestamp":1712188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Elisabeth and Karl Ejnar Nis-Hanssens"},{"name":"Beckett Foundation"},{"name":"Heinrich Kopps Scholarship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>(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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Six female pigs received an intravenous single dose of moxifloxacin (6\u2005mg\/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 &amp;gt;8.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We present a novel porcine model for continuous in vivo CNS pharmacokinetics for moxifloxacin. Cmax and AUC0\u20138h 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkae098","type":"journal-article","created":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T17:34:39Z","timestamp":1712252079000},"page":"1313-1319","source":"Crossref","is-referenced-by-count":6,"title":["Continuous evaluation of single-dose moxifloxacin concentrations in brain extracellular fluid, cerebrospinal fluid, and plasma: a novel porcine 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Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"\u00d6brink-Hansen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Internal Medicine, G\u00f8dstrup Hospital , Herning , Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Nau","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, University Medical Center , G\u00f6ttingen , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C R","family":"Bjarkam","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Aalborg University Hospital , Aalborg , Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0841-8255","authenticated-orcid":false,"given":"H","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Aalborg University Hospital , Aalborg , Denmark"},{"name":"Department of 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