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Linezolid pharmacokinetics have not been characterized in this population, particularly in cerebrospinal fluid (CSF), as well as, following its co-administration with high-dose rifampicin. We aimed to characterize linezolid plasma and CSF pharmacokinetics in adults with TBM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In the LASER-TBM pharmacokinetic substudy, the intervention groups received high-dose rifampicin (35\u2005mg\/kg) plus 1200\u2005mg\/day of linezolid for 28 days, which was then reduced to 600\u2005mg\/day. Plasma sampling was done on day 3 (intensive) and day 28 (sparse). A lumbar CSF sample was obtained on both visits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirty participants contributed 247 plasma and 28 CSF observations. Their median age and weight were 40 years (range, 27\u201356) and 58 kg (range, 30\u201396). Plasma pharmacokinetics was described by a 1-compartment model with first-order absorption and saturable elimination. Maximal clearance was 7.25 L\/h, and the Michaelis-Menten constant was 27.2\u2005mg\/L. Rifampicin cotreatment duration did not affect linezolid pharmacokinetics. CSF-plasma partitioning correlated with CSF total protein up to 1.2\u2005g\/L, where the partition coefficient reached a maximal value of 37%. The plasma-CSF equilibration half-life was \u223c3.5 hours.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Linezolid was readily detected in CSF despite high-dose rifampicin coadministration. These findings support continued clinical evaluation of linezolid plus high-dose rifampicin for the treatment of TBM in adults.<\/jats:p>\n                    <jats:p>Clinical Trials Registration. \u2003ClinicalTrials.gov (NCT03927313).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiad413","type":"journal-article","created":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T16:28:48Z","timestamp":1695227328000},"page":"1200-1208","source":"Crossref","is-referenced-by-count":17,"title":["Linezolid Population Pharmacokinetic Model in Plasma and Cerebrospinal Fluid Among Patients With Tuberculosis Meningitis"],"prefix":"10.1093","volume":"229","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4907-345X","authenticated-orcid":false,"given":"Noha","family":"Abdelgawad","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, South 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