Trial reportThe Journal of infectious diseases2025
Population Pharmacokinetics of Rifampicin in Plasma and Cerebrospinal Fluid in Adults With Tuberculosis Meningitis.
Trial report in The Journal of infectious diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
5 citing papers in PubMed.
- Population Pharmacokinetic Modeling of Standard- and High-Dose Rifampicin for Tuberculosis Preventive Therapy in the 2R2 Randomized Controlled Trial.The Journal of infectious diseases · 2026Trial
- Central nervous system antituberculosis drug exposures in a rabbit model of tuberculous meningitis.Antimicrobial agents and chemotherapy · 2026Article
- Drug repurposing for disease-modifying effects in multiple system atrophy.Translational neurodegeneration · 2026Review
- Review
- Host- and pathogen-related determinants of pulmonaryEuropean respiratory review : an official journal of the European Respiratory Society · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
backgroundSeveral ongoing clinical trials are evaluating high-dose rifampicin (up to 35 mg/kg) for tuberculous meningitis (TBM). However, rifampicin pharmacokinetics at higher doses is not fully characterized, particularly in cerebrospinal fluid (CSF), the site of TBM disease.
methodsIn a randomized controlled trial, adults with HIV-associated TBM were assigned to experimental arms of high-dose rifampicin (oral, 35 mg/kg; intravenous, 20 mg/kg) plus linezolid, with or without aspirin, or a control arm that received the standard of care with 10 mg/kg of oral rifampicin. Rifampicin concentrations, including the unbound fraction, were measured on plasma samples, and CSF was collected on days 3 and 28 of study enrollment. Data were analyzed by nonlinear mixed effects modeling.
resultsIn total, 400 plasma and 44 CSF rifampicin concentrations from 48 participants were used for model development. The median (range) age and weight were 39 years (25-78) and 60 kg (30-107). Rifampicin pharmacokinetics was best described by a 2-compartment disposition model with first-order transit oral absorption and elimination via saturable hepatic extraction. Typical clearance values for the standard dose for days 3 and 28 were 33.1 and 41.4 L/h, respectively; high-dose values were 46.1 and 70.2 L/h. The CSF-plasma ratio was approximately 6% and the equilibration half-life was 3.2 hours. Simulated standard-dose rifampicin did not reach CSF concentrations above the critical concentration for Mycobacterium tuberculosis.
conclusionsCSF penetration with standard-dose rifampicin is low. Our findings support continued evaluation of high-dose rifampicin for TBM treatment.
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