ArticleAntimicrobial agents and chemotherapy2023
Population Pharmacokinetic Analysis of Rifampicin in Plasma, Cerebrospinal Fluid, and Brain Extracellular Fluid in South African Children with Tuberculous Meningitis.
Article in Antimicrobial agents and chemotherapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
6 citing papers in PubMed, 8 citations in OpenAlex.
- Population Pharmacokinetics of Rifampicin in Plasma and Cerebrospinal Fluid in Adults With Tuberculosis Meningitis.The Journal of infectious diseases · 2025Trial
- Central nervous system antituberculosis drug exposures in a rabbit model of tuberculous meningitis.Antimicrobial agents and chemotherapy · 2026Article
- Beyond Rifampin: Evaluating Rifapentine and Rifabutin as Alternative Treatments for Tuberculous Meningitis.The Journal of infectious diseases · 2026Article
- Pharmacokinetic approaches to standardize antiviral exposure in cerebrospinal fluid.Pharmacotherapy · 2025Article
- In-vitro and in-vivo assessment of nirmatrelvir penetration into CSF, central nervous system cells, tissues, and peripheral blood mononuclear cells.Scientific reports · 2024Article
- A preclinical model of TB meningitis to determine drug penetration and activity at the sites of disease.Antimicrobial agents and chemotherapy · 2023Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Limited knowledge is available on the pharmacokinetics of rifampicin in children with tuberculous meningitis (TBM) and its penetration into brain tissue, which is the site of infection. In this analysis, we characterize the distribution of rifampicin in cerebrospinal fluid (CSF), lumbar (LCSF) and ventricular (VCSF), and brain extracellular fluid (ECF). Children with TBM were included in this pharmacokinetic analysis. Sparse plasma, LCSF, and VCSF samples were collected opportunistically, as clinically indicated. Brain ECF was sampled using microdialysis (MD). Rifampicin was quantified with liquid chromatography with tandem mass spectrometry in all samples, and 25-desacetyl rifampicin in the plasma samples. The data were interpreted with nonlinear mixed-effects modeling, with the CSF and brain ECF modeled as "effect compartments." Data were available from 61 children, with median (min-max) age of 2 (0.3 to 10) years and weight of 11.0 (4.8 to 49.0) kg. A one-compartment model for parent and metabolite with first-order absorption and elimination via saturable hepatic clearance described the data well. Allometric scaling, maturation, and auto-induction of clearance were included. The pseudopartition coefficient between plasma and LCSF/VCSF was ~5%, while the value for ECF was only ~0.5%, possibly reflecting low recovery of rifampicin using MD. The equilibration half-life between plasma and LCSF/VCSF was ~4 h and between plasma and ECF ~2 h. Our study confirms previous reports showing that rifampicin concentrations in the LCSF are lower than in plasma and provides novel knowledge about rifampicin in the VCSF and the brain tissue. Despite MD being semiquantitative because the relative recovery cannot be quantified, our study presents a proof-of-concept that rifampicin reaches the brain tissue and that MD is an attractive technique to study site-of-disease pharmacokinetics in TBM.
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Registered trials
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