ArticleThe Journal of antimicrobial chemotherapy2014
Population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children with tuberculosis: in silico evaluation of currently recommended doses.
Article in The Journal of antimicrobial chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
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
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 62 citations in OpenAlex.
- A systematic review and meta-analysis of first-line tuberculosis drug concentrations and treatment outcomes.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2020Pooled it
- Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2016Guideline
- Optimization of dosing regimens of isoniazid and rifampicin in children with tuberculosis in India.British journal of clinical pharmacology · 2019Trial
- Extrapolation of praziquantel pharmacokinetics to a pediatric population: a cautionary tale.Journal of pharmacokinetics and pharmacodynamics · 2018Trial
- Population Pharmacokinetics of the Antimalarial Amodiaquine: a Pooled Analysis To Optimize Dosing.Antimicrobial agents and chemotherapy · 2018Trial
- Evaluation of the Adequacy of WHO Revised Dosages of the First-Line Antituberculosis Drugs in Children with Tuberculosis Using Population Pharmacokinetic Modeling and Simulations.Antimicrobial agents and chemotherapy · 2018Trial
- Application of Pharmacometric Modelling Towards Precise Dosing in Neonates, Infants and Toddlers: A Scoping Review.Clinical pharmacokinetics · 2026Review
- Population pharmacokinetics of pyrazinamide and ethambutol in children with tuberculosis with or without HIV.Antimicrobial agents and chemotherapy · 2026Article
- Multidimensional analysis of clinical pharmacist intervention impact on hospital length of stay in pulmonary tuberculosis: a random forest-driven retrospective study.BMC infectious diseases · 2026Article
- Parametric Population Pharmacokinetics Model Repository of Rifampicin: Model-Informed Individualized Therapy.Clinical pharmacology : advances and applications · 2025Article
- Optimized Sampling Strategies for Isoniazid in East Asian Pediatric Populations Using Population Pharmacokinetics-Informed Approaches.Drug design, development and therapy · 2025Article
- Leveraging physiologically based pharmacokinetic modeling to optimize dosing for lopinavir/ritonavir with rifampin in pediatric patients.Pharmacotherapy · 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
- Development of a population pharmacokinetic model of pyrazinamide to guide personalized therapy: impacts of geriatric and diabetes mellitus on clearance.Frontiers in pharmacology · 2023Article
- 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
- Optimizing Dosing and Fixed-Dose Combinations of Rifampicin, Isoniazid, and Pyrazinamide in Pediatric Patients With Tuberculosis: A Prospective Population Pharmacokinetic Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- Drug concentration at the site of disease in children with pulmonary tuberculosis.The Journal of antimicrobial chemotherapy · 2022Article
- Pharmacokinetics and pharmacodynamics of anti-tuberculosis drugs: An evaluation ofFrontiers in pharmacology · 2022Review
- 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
objectivesTo describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children and evaluate the adequacy of steady-state exposures. PATIENTS AND
methodsWe used previously published data for 76 South African children with tuberculosis to describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid. Monte Carlo simulations were used to predict steady-state exposures in children following doses in fixed-dose combination tablets in accordance with the revised guidelines. Reference exposures were derived from an ethnically similar adult population with tuberculosis taking currently recommended doses.
resultsThe final models included allometric scaling of clearance and volume of distribution using body weight. Maturation was included for clearance of isoniazid and clearance and absorption transit time of rifampicin. For a 2-year-old child weighing 12.5 kg, the estimated typical oral clearances of rifampicin and pyrazinamide were 8.15 and 1.08 L/h, respectively. Isoniazid typical oral clearance (adjusted for bioavailability) was predicted to be 4.44, 11.6 and 14.6 L/h for slow, intermediate and fast acetylators, respectively. Higher oral clearance values in intermediate and fast acetylators also resulted from 23% lower bioavailability compared with slow acetylators.
conclusionsSimulations based on our models suggest that with the new WHO dosing guidelines and utilizing available paediatric fixed-dose combinations, children will receive adequate rifampicin exposures when compared with adults, but with a larger degree of variability. However, pyrazinamide and isoniazid exposures in many children will be lower than in adults. Further studies are needed to confirm these findings in children administered the revised dosages and to optimize pragmatic approaches to dosing.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.