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Co-administration with rifampicin is expected to reduce dexamethasone exposure in TBM, an effect that may be more pronounced with the higher rifampicin doses currently being evaluated in clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This pharmacokinetic study was nested in a randomized controlled trial comparing the safety of high-dose rifampicin (oral, 35\u2005mg\/kg; intravenous, 20\u2005mg\/kg) plus linezolid, with or without aspirin, versus standard-dose rifampicin (10\u2005mg\/kg) for adults with HIV-associated TBM. All participants received adjunctive oral dexamethasone every 12\u2005hours starting at a dose of 0.4\u2005mg\/kg\/day. Dexamethasone concentrations were measured on intensively sampled plasma on day 3 after study enrollment and analysed using nonlinear mixed-effects modeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In total, 261 dexamethasone concentrations from 43 participants were available for model development. Eight (18%) participants were on efavirenz-based ART and five (11%) were on a lopinavir\/ritonavir-based regimen. The median duration of rifampicin therapy at the time of pharmacokinetic sampling was 4 days (range: 0\u20137). Dexamethasone pharmacokinetics was best described by a one-compartment disposition model with first-order absorption and elimination. Typical oral clearance (CL\/F) was 131 L\/h, reduced to 11.5 L\/h with concomitant lopinavir\/ritonavir. High-dose rifampicin had no significant additional effect on dexamethasone pharmacokinetic parameters compared with the standard-dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In adults with HIV-associated TBM, there was high dexamethasone clearance, likely related to a drug-drug interaction with rifampicin. High-dose rifampicin had no additional effect on dexamethasone exposure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciaf642","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T13:07:55Z","timestamp":1765372075000},"page":"e1036-e1042","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacokinetics of Dexamethasone in Tuberculous Meningitis"],"prefix":"10.1093","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0310-6949","authenticated-orcid":false,"given":"Jose M","family":"Calderin","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Observatory , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9111-8052","authenticated-orcid":false,"given":"Juan Eduardo","family":"Resendiz-Galvan","sequence":"additional","affiliation":[{"name":"Division of 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