ArticleThe Journal of antimicrobial chemotherapy2021
Pharmacokinetics and safety of high-dose rifampicin in children with TB: the Opti-Rif trial.
Article in The Journal of antimicrobial chemotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 3 of them syntheses that pooled it.
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
22 citing papers in PubMed, 3 syntheses or guidelines pooled it, 43 citations in OpenAlex.
- A clinical practice guideline for tuberculous meningitis.The Lancet. Infectious diseases · 2026Guideline
- Effectiveness and Pharmacokinetic Exposures of First-Line Drugs Used to Treat Drug-Susceptible Tuberculosis in Children: A Systematic Review and Meta-Analysis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Pooled it
- Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis.The European respiratory journal · 2023Pooled it
- 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
- Intensified Treatment of Tuberculous Meningitis in Adults: A Systematic Review and Meta-analysis.Open forum infectious diseases · 2025Trial
- Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Trial
- Clinical characteristics of childhood tuberculous meningitis and risk factors for severe neurological sequelae disaggregated by age group.BMC infectious diseases · 2026Article
- Analysis of factors influencing plasma concentrations of anti-TB drugs in pediatric TB patients.BMC infectious diseases · 2025Article
- Article
- Evaluating the efficacy of HRZE-based regimens in a high-burden murine model: a back-translational assessment of rifamycins and moxifloxacin substitutions in tuberculosis treatment.Frontiers in pharmacology · 2025Article
- The impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs.The Journal of antimicrobial chemotherapy · 2024Article
- Variability in plasma rifampicin concentrations and role ofInfectious diseases (London, England) · 2024Article
- Evaluating pediatric tuberculosis dosing guidelines: A model-based individual data pooled analysis.PLoS medicine · 2023Article
- Rifampin urinary excretion to predict serum targets in children with tuberculosis: a prospective diagnostic accuracy study.Archives of disease in childhood · 2023Article
- Population Pharmacokinetic Analysis of Rifampicin in Plasma, Cerebrospinal Fluid, and Brain Extracellular Fluid in South African Children with Tuberculous Meningitis.Antimicrobial agents and chemotherapy · 2023Article
- New and Repurposed Drugs for the Treatment of Active Tuberculosis: An Update for Clinicians.Respiration; international review of thoracic diseases · 2023Review
- Pharmacokinetic study of high-dose oral rifampicin in critically Ill patients with multidrug-resistant Acinetobacter baumannii infection.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2022Article
- Childhood Tuberculosis: Historical Perspectives, Recent Advances, and a Call to Action.Journal of the Pediatric Infectious Diseases Society · 2022Article
- Drug concentration at the site of disease in children with pulmonary tuberculosis.The Journal of antimicrobial chemotherapy · 2022Article
- High-dose rifampin improves bactericidal activity without increased intracerebral inflammation in animal models of tuberculous meningitis.The Journal of clinical investigation · 2022Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundRifampicin doses of 40 mg/kg in adults are safe and well tolerated, may shorten anti-TB treatment and improve outcomes, but have not been evaluated in children.
objectivesTo characterize the pharmacokinetics and safety of high rifampicin doses in children with drug-susceptible TB. PATIENTS AND
methodsThe Opti-Rif trial enrolled dosing cohorts of 20 children aged 0-12 years, with incremental dose escalation with each subsequent cohort, until achievement of target exposures or safety concerns. Cohort 1 opened with a rifampicin dose of 15 mg/kg for 14 days, with a single higher dose (35 mg/kg) on day 15. Pharmacokinetic data from days 14 and 15 were analysed using population modelling and safety data reviewed. Incrementally increased rifampicin doses for the next cohort (days 1-14 and day 15) were simulated from the updated model, up to the dose expected to achieve the target exposure [235 mg/L·h, the geometric mean area under the concentration-time curve from 0 to 24 h (AUC0-24) among adults receiving a 35 mg/kg dose].
resultsSixty-two children were enrolled in three cohorts. The median age overall was 2.1 years (range = 0.4-11.7). Evaluated doses were ∼35 mg/kg (days 1-14) and ∼50 mg/kg (day 15) for cohort 2 and ∼60 mg/kg (days 1-14) and ∼75 mg/kg (day 15) for cohort 3. Approximately half of participants had an adverse event related to study rifampicin; none was grade 3 or higher. A 65-70 mg/kg rifampicin dose was needed in children to reach the target exposure.
conclusionsHigh rifampicin doses in children achieved target exposures and the doses evaluated were safe over 2 weeks.
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Registered trials
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