ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2022
Optimizing Dosing and Fixed-Dose Combinations of Rifampicin, Isoniazid, and Pyrazinamide in Pediatric Patients With Tuberculosis: A Prospective Population Pharmacokinetic Study.
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 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- 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
- Bridging to Paediatric Dosing: Relative Bioavailability of Suspended Rifapentine and Isoniazid in an Open-Label Randomized Trial in Adults on Tuberculosis Preventive Therapy.Clinical pharmacokinetics · 2025Trial
- Article
- Bard1-Mediated Regulation of Hnrnpa2b1 Ubiquitination and Protein Stability Contributes to Neuronal Ferroptosis and Cognitive Dysfunction Following Ischemic Stroke.CNS neuroscience & therapeutics · 2026Article
- Population pharmacokinetics of pyrazinamide and ethambutol in children with tuberculosis with or without HIV.Antimicrobial agents and chemotherapy · 2026Article
- Investigation of potential relationship betweenmazEF3, relJK, and vapBC3 genes and antimicrobial resistance inMycobacterium bovis.BMC infectious diseases · 2025Article
- Three-Dimensional-Printed Isoniazid Chewable Gels for On-Demand Latent Tuberculosis Treatment in Children.Pharmaceutics · 2025Article
- Pharmacokinetic Analysis of an Isoniazid Suspension Among Spanish Children Under 6 Years of Age.Antibiotics (Basel, Switzerland) · 2025Article
- Parametric Population Pharmacokinetics Model Repository of Rifampicin: Model-Informed Individualized Therapy.Clinical pharmacology : advances and applications · 2025Article
- Pyrazine derivative synthesis in a continuous-flow system: a green synthesis of pyrazinamide from pyrazine esters and amines catalyzed by Lipozyme® TL IM fromRSC advances · 2024Article
- Pharmacokinetics and pharmacodynamics of high-dose isoniazid for the treatment of rifampicin- or multidrug-resistant tuberculosis in Indonesia.The Journal of antimicrobial chemotherapy · 2024Observational
- Model-Informed Precision Dosing of Isoniazid: Parametric Population Pharmacokinetics Model Repository.Drug design, development and therapy · 2024Article
- Distribution of lineages and type II toxin-antitoxin systems among rifampin-resistant Mycobacterium Tuberculosis Isolates.PloS one · 2024Article
- Evaluating pediatric tuberculosis dosing guidelines: A model-based individual data pooled analysis.PLoS medicine · 2023Article
- Modular Titratable Polypills for Personalized Medicine and Simplification of Complex Medication Regimens.Advanced healthcare materials · 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
- 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
- Adequacy of the 10 mg/kg Daily Dose of Antituberculosis Drug Isoniazid in Infants under 6 Months of Age.Antibiotics (Basel, Switzerland) · 2023Article
- Zebrafish in dermatology: a comprehensive review of their role in investigating abnormal skin pigmentation mechanisms.Frontiers in physiology · 2023Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 6 countries.
Funding
Abstract
backgroundIn 2010, the World Health Organization (WHO) revised dosing guidelines for treatment of childhood tuberculosis. Our aim was to investigate first-line antituberculosis drug exposures under these guidelines, explore dose optimization using the current dispersible fixed-dose combination (FDC) tablet of rifampicin/isoniazid/pyrazinamide; 75/50/150 mg, and suggest a new FDC with revised weight bands.
methodsChildren with drug-susceptible tuberculosis in Malawi and South Africa underwent pharmacokinetic sampling while receiving first-line tuberculosis drugs as single formulations according the 2010 WHO recommended doses. Nonlinear mixed-effects modeling and simulation was used to design the optimal FDC and weight-band dosing strategy for achieving the pharmacokinetic targets based on literature-derived adult AUC0-24h for rifampicin (38.7-72.9), isoniazid (11.6-26.3), and pyrazinamide (233-429 mg ∙ h/L).
resultsIn total, 180 children (42% female; 13.9% living with human immunodeficiency virus [HIV]; median [range] age 1.9 [0.22-12] years; weight 10.7 [3.20-28.8] kg) were administered 1, 2, 3, or 4 FDC tablets (rifampicin/isoniazid/pyrazinamide 75/50/150 mg) daily for 4-8, 8-12, 12-16, and 16-25 kg weight bands, respectively. Rifampicin exposure (for weight and age) was up to 50% lower than in adults. Increasing the tablet number resulted in adequate rifampicin but relatively high isoniazid and pyrazinamide exposures. Administering 1, 2, 3, or 4 optimized FDC tablets (rifampicin/isoniazid/pyrazinamide 120/35/130 mg) to children < 6, 6-13, 13-20. and 20-25 kg, and 0.5 tablet in < 3-month-olds with immature metabolism, improved exposures to all 3 drugs.
conclusionsCurrent pediatric FDC doses resulted in low rifampicin exposures. Optimal dosing of all drugs cannot be achieved with the current FDCs. We propose a new FDC formulation and revised weight bands.
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