Observational studyThe Journal of antimicrobial chemotherapy2015
Subtherapeutic concentrations of first-line anti-TB drugs in South African children treated according to current guidelines: the PHATISA study.
Observational study in The Journal of antimicrobial chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 4 of them syntheses 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
33 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Pharmacokinetics and Dose Optimization of Ethambutol in Children on First-Line Antituberculosis Therapy: An Individual Patient Data Meta-Analysis.The Journal of infectious diseases · 2026Pooled 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
- Pharmacokinetics of antiretroviral and tuberculosis drugs in children with HIV/TB co-infection: a systematic review.The Journal of antimicrobial chemotherapy · 2020Pooled it
- A Systematic Review on the Effect of HIV Infection on the Pharmacokinetics of First-Line Tuberculosis Drugs.Clinical pharmacokinetics · 2019Pooled it
- 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
- Fractal Geometry-Based Decrease in Trimethoprim-Sulfamethoxazole Concentrations in Overweight and Obese People.CPT: pharmacometrics & systems pharmacology · 2016Trial
- Pharmacokinetics of Rifampin, Isoniazid, Pyrazinamide, and Ethambutol in Infants Dosed According to Revised WHO-Recommended Treatment Guidelines.Antimicrobial agents and chemotherapy · 2016Trial
- Ethambutol Population Pharmacokinetics and Pharmacodynamics From a Phase 3 Confirmatory Trial for the Treatment of Tuberculosis.The Journal of infectious diseases · 2026Article
- 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 pharmacokinetics of ethambutol in African children: a pooled analysis.The Journal of antimicrobial chemotherapy · 2022Article
- Drug concentration at the site of disease in children with pulmonary tuberculosis.The Journal of antimicrobial chemotherapy · 2022Article
- Four months of rifampicin monotherapy for latent tuberculosis infection in children.Clinical and experimental pediatrics · 2022Article
- Pharmacokinetics and safety of high-dose rifampicin in children with TB: the Opti-Rif trial.The Journal of antimicrobial chemotherapy · 2021Article
- Population Pharmacokinetics and Bayesian Dose Adjustment to Advance TDM of Anti-TB Drugs.Clinical pharmacokinetics · 2021Review
- The Bewildering Antitubercular Action of Pyrazinamide.Microbiology and molecular biology reviews : MMBR · 2020Review
- Pharmacokinetics of First-Line Drugs Among Children With Tuberculosis in Rural Tanzania.Journal of the Pediatric Infectious Diseases Society · 2020Article
- Pharmacokinetics of First-Line Anti-Tubercular Drugs.Indian journal of pediatrics · 2019Review
- Current research toward optimizing dosing of first-line antituberculosis treatment.Expert review of anti-infective therapy · 2019Review
- NoninvasiveScience translational medicine · 2018Article
- HIV-associated pediatric tuberculosis: prevention, diagnosis and treatment.Current opinion in HIV and AIDS · 2018Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
objectivesThere is a paucity of evidence regarding the optimal dosing of anti-TB drugs in children. The aim of this study was to identify the pharmacokinetic parameters of first-line anti-TB drugs and the concentrations achieved after implementation of the 2010 WHO-recommended paediatric dosages.
methodsWe conducted a prospective, observational pharmacokinetic study in children 10 years old or younger who were on isoniazid, rifampicin, pyrazinamide and ethambutol therapy in Durban, KwaZulu-Natal, South Africa. Blood was collected at six timepoints over a 24 h period, chosen using optimal sampling theory. The drug concentrations were simultaneously modelled to identify the compartmental pharmacokinetics of each drug in each child, using the ADAPT program.
resultsThe best six sampling timepoints in children were identified as 0 (pre-dose) and 0.42, 1.76, 3.37, 10.31 and 24 h post-dose. Thirty-one children were recruited and blood was drawn at these timepoints. Rifampicin, ethambutol and pyrazinamide were best described using a one-compartment model, while isoniazid was best described with a two-compartment model. Only 2/31 (6%), 20/31 (65%), 17/31 (55%) and 2/13 (15%) of children attained the WHO 2 h target therapeutic concentrations of rifampicin, isoniazid, pyrazinamide and ethambutol, respectively. Moreover, only 24/31 (77%), 6/31 (19%) and 8/31 (26%) achieved the AUCs associated with an optimal clinical response to rifampicin, pyrazinamide and isoniazid, respectively. No single risk factor was significantly associated with below-normal drug levels.
conclusionsThe drug concentrations of all first-line anti-TB drugs were markedly below the target therapeutic concentrations in most South African children who received the revised WHO-recommended paediatric weight-based dosages.
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