Trial reportBritish journal of clinical pharmacology2019
Optimization of dosing regimens of isoniazid and rifampicin in children with tuberculosis in India.
Trial report in British journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Influence of N-acetyltransferase 2 (NAT2) genotype/single nucleotide polymorphisms on clearance of isoniazid in tuberculosis patients: a systematic review of population pharmacokinetic models.European journal of clinical pharmacology · 2022Pooled it
- Optimization of dosing regimens of isoniazid and rifampicin in children with tuberculosis in India.British journal of clinical pharmacology · 2019Trial
- Regimen-Specific Population Pharmacokinetics of Isoniazid with and Without Rifamycin: A Bayesian Modeling Analysis of 6H, 3HR, and 3H2P2 Regimens.Pharmaceutics · 2026Article
- Optimized Sampling Strategies for Isoniazid in East Asian Pediatric Populations Using Population Pharmacokinetics-Informed Approaches.Drug design, development and therapy · 2025Article
- Parametric Population Pharmacokinetics Model Repository of Rifampicin: Model-Informed Individualized Therapy.Clinical pharmacology : advances and applications · 2025Article
- New and Repurposed Drugs for the Treatment of Active Tuberculosis: An Update for Clinicians.Respiration; international review of thoracic diseases · 2023Review
- Influence of NAT2 Genotype and Maturation on Isoniazid Exposure in Low-Birth-Weight and Preterm Infants With or Without Human Immunodeficiency Virus (HIV) Exposure.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- Four months of rifampicin monotherapy for latent tuberculosis infection in children.Clinical and experimental pediatrics · 2022Article
- Population Pharmacokinetics and Pharmacodynamics of Isoniazid and its Metabolite Acetylisoniazid in Chinese Population.Frontiers in pharmacology · 2022Article
- Evaluation of the estimation and classification performance of NONMEM when applying mixture model for drug clearance.CPT: pharmacometrics & systems pharmacology · 2021Article
- Population Pharmacokinetics and Bayesian Dose Adjustment to Advance TDM of Anti-TB Drugs.Clinical pharmacokinetics · 2021Review
- Population Pharmacokinetic Properties of Antituberculosis Drugs in Vietnamese Children with Tuberculous Meningitis.Antimicrobial agents and chemotherapy · 2020Article
- Pharmacokinetics of First-Line Anti-Tubercular Drugs.Indian journal of pediatrics · 2019Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsPharmacokinetic studies in the past have shown inadequate antituberculosis drug levels in children with the currently available dosing regimens. This study attempted to investigate the pharmacokinetics of isoniazid and rifampicin, when used in children, and to optimize their dosing regimens.
methodsData were collected from 41 children, aged 2-16 years, who were being treated with antituberculosis drugs for at least 2 months. Concentration measurements were done for 6 h and analysed using a nonlinear, mixed-effects model.
resultsIsoniazid pharmacokinetics were described by a one-compartment disposition model with a transit absorption model (fixed, n = 5). A mixture model was used to identify the slow and fast acetylator subgroups. Rifampicin was described by a one-compartment disposition model with a transit absorption model (fixed, n = 9). Body weight was added to the clearance and volume of distribution of both the drugs using an allometric function. Simulations with the isoniazid model showed that 84.9% of the population achieved therapeutic peak serum concentration with the planned fixed-dose combination regimen. Simulations with the rifampicin model showed that only about 28.8% of the simulated population achieve the therapeutic peak serum concentration with the fixed-dose combination regimen. A novel regimen for rifampicin, with an average dose of 35 mg kg
conclusionsThe exposure to isoniazid is adequate with present regimens. For rifampicin, a novel dosing regimen was developed to ensure adequate drug concentrations in children. However, further studies are required to assess the dose-effect relationship of higher doses of rifampicin.
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