Observational studyThe Pediatric infectious disease journal2018
Evaluation of the Adequacy of the 2010 Revised World Health Organization Recommended Dosages of the First-line Antituberculosis Drugs for Children: Adequacy of Revised Dosages of TB Drugs for Children.
Observational study in The Pediatric infectious disease journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pharmacokinetics of antiretroviral and tuberculosis drugs in children with HIV/TB co-infection: a systematic review.The Journal of antimicrobial chemotherapy · 2020Pooled 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
- 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
- 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
- Pediatric Tuberculosis Management: A Global Challenge or Breakthrough?Children (Basel, Switzerland) · 2022Review
- Pharmacokinetics of First-Line Drugs in Children With Tuberculosis, Using World Health Organization-Recommended Weight Band Doses and Formulations.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- Article
- Pharmacokinetics of First-Line Drugs Among Children With Tuberculosis in Rural Tanzania.Journal of the Pediatric Infectious Diseases Society · 2020Article
- Alternative dosing guidelines to improve outcomes in childhood tuberculosis: a mathematical modelling study.The Lancet. Child & adolescent health · 2019Article
- Pharmacokinetics of First-Line Anti-Tubercular Drugs.Indian journal of pediatrics · 2019Review
- 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
11 authors.
Funding
Abstract
backgroundThe World Health Organization recommended increased dosages of the first-line antituberculosis (anti-TB) drugs for children in 2010. We examined the frequency of and factors associated with low plasma maximum concentration (Cmax) of each drug in children treated with the revised dosages.
methodsChildren on anti-TB therapy for at least 4 weeks underwent pharmacokinetic testing. Plasma Cmax below the lower limit of proposed reference range was considered low. Bivariate and multivariate analyses were used to examine the factors associated with low Cmax of each drug.
resultsOf the 100 children, 58% were male, 50% HIV-infected and 49% younger than 5 years old. The median (interquartile range) Cmax was 5.9 (4.5-7.7) µg/mL for isoniazid, 6.5 (4.9-8.8) µg/mL for rifampin, 26.0 (21.2-33.4) µg/mL for pyrazinamide and 1.7 (0.9-2.7) µg/mL for ethambutol. There was a strong correlation between Cmax and AUC0-8h for all drugs. Low Cmax occurred in 9/100 (9.0%), 61/100 (61.0%), 17/97 (17.5%) and 60/97 (61.9%) for isoniazid, rifampin, pyrazinamide and ethambutol, respectively. In addition, 75/97 (77.3%) children had pyrazinamide Cmax < 35 µg/mL. Factors associated with low Cmax were NAT2 metabolizer phenotype status for isoniazid; height, dosage and HIV coinfection status for rifampin; height for pyrazinamide; and age, dosage and HIV coinfection status for ethambutol.
conclusionsThe high frequency of low rifampin and ethambutol Cmax in our study is consistent with emerging pharmacokinetic data in children treated according to the new WHO recommendations. Higher dosages than currently recommended especially for rifampin may be necessary in children.
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