ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2022
Pharmacokinetics of First-Line Drugs in Children With Tuberculosis, Using World Health Organization-Recommended Weight Band Doses and Formulations.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 4 of them syntheses that pooled it.
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Who cites it
23 citing papers in PubMed, 4 syntheses or guidelines pooled it, 31 citations in OpenAlex.
- A clinical practice guideline for tuberculous meningitis.The Lancet. Infectious diseases · 2026Guideline
- Rifampicin Exposure in Tuberculosis Patients with Comorbidities in Sub-Saharan Africa: Prioritising Populations for Treatment-A Systematic Review and Meta-analysis.Clinical pharmacokinetics · 2025Pooled it
- 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
- Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial.The lancet. HIV · 2022Trial
- Article
- Population pharmacokinetics of pyrazinamide and ethambutol in children with tuberculosis with or without HIV.Antimicrobial agents and chemotherapy · 2026Article
- Clinical characteristics of childhood tuberculous meningitis and risk factors for severe neurological sequelae disaggregated by age group.BMC infectious diseases · 2026Article
- Tuberculosis disease among people with HIV: therapeutic advances.The lancet. HIV · 2025Review
- Pharmacokinetic Analysis of an Isoniazid Suspension Among Spanish Children Under 6 Years of Age.Antibiotics (Basel, Switzerland) · 2025Article
- Precision dosing of voriconazole in immunocompromised children under 2 years: integrated machine learning and population pharmacokinetic modeling.Frontiers in pharmacology · 2025Article
- Precision Medicine Strategies to Improve Isoniazid Therapy in Patients with Tuberculosis.European journal of drug metabolism and pharmacokinetics · 2024Review
- Leading Paediatric Infectious Diseases-Current Trends, Gaps, and Future Prospects in Oral Pharmacotherapeutic Interventions.Pharmaceutics · 2024Review
- Effect of HIV infection on plasma exposure to first-line TB drugs and target attainment in children.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2023Article
- First-Line Antituberculosis Drug Concentrations in Infants With HIV and a History of Recent Admission With Severe Pneumonia.Journal of the Pediatric Infectious Diseases Society · 2023Article
- Evaluating pediatric tuberculosis dosing guidelines: A model-based individual data pooled analysis.PLoS medicine · 2023Article
- Adequacy of WHO weight-band dosing and fixed-dose combinations for the treatment of TB in children.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2023Article
- Adequacy of the 10 mg/kg Daily Dose of Antituberculosis Drug Isoniazid in Infants under 6 Months of Age.Antibiotics (Basel, Switzerland) · 2023Article
- Development of a population pharmacokinetic model of pyrazinamide to guide personalized therapy: impacts of geriatric and diabetes mellitus on clearance.Frontiers in pharmacology · 2023Article
- A Micro-Configured Multiparticulate Reconstitutable Suspension Powder of Fixed Dose Rifampicin and Pyrazinamide: Optimal Fabrication and In Vitro Quality Evaluation.Pharmaceutics · 2022Article
Corrections and comments
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Authors and funding
19 authors at 8 institutions in 6 countries.
Funding
Abstract
backgroundDispersible pediatric fixed-dose combination (FDC) tablets delivering higher doses of first-line antituberculosis drugs in World Health Organization-recommended weight bands were introduced in 2015. We report the first pharmacokinetic data for these FDC tablets in Zambian and South African children in the treatment-shortening SHINE trial.
methodsChildren weighing 4.0-7.9, 8.0-11.9, 12.0-15.9, or 16.0-24.9 kg received 1, 2, 3, or 4 tablets daily, respectively (rifampicin/isoniazid/pyrazinamide [75/50/150 mg], with or without 100 mg ethambutol, or rifampicin/isoniazid [75/50 mg]). Children 25.0-36.9 kg received doses recommended for adults <37 kg (300, 150, 800, and 550 mg/d, respectively, for rifampicin, isoniazid, pyrazinamide, and ethambutol). Pharmacokinetics were evaluated after at least 2 weeks of treatment.
resultsIn the 77 children evaluated, the median age (interquartile range) was 3.7 (1.4-6.6) years; 40 (52%) were male and 20 (26%) were human immunodeficiency virus positive. The median area under the concentration-time curve from 0 to 24 hours for rifampicin, isoniazid, pyrazinamide, and ethambutol was 32.5 (interquartile range, 20.1-45.1), 16.7 (9.2-25.9), 317 (263-399), and 9.5 (7.5-11.5) mg⋅h/L, respectively, and lower in children than in adults for rifampicin in the 4.0-7.9-, 8-11.9-, and ≥25-kg weight bands, isoniazid in the 4.0-7.9-kg and ≥25-kg weight bands, and ethambutol in all 5 weight bands. Pyrazinamide exposures were similar to those in adults.
conclusionsRecommended weight band-based FDC doses result in lower drug exposures in children in lower weight bands and in those ≥25 kg (receiving adult doses). Further adjustments to current doses are needed to match current target exposures in adults. The use of ethambutol at the current World Health Organization-recommended doses requires further evaluation.
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