ArticleBMC infectious diseases2015
Pharmacokinetics of isoniazid, rifampicin, pyrazinamide and ethambutol in Indian children.
Article in BMC infectious diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 5 of them syntheses that pooled it.
What it found
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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
22 citing papers in PubMed, 5 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- 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
- Efficacy, safety, and pharmacokinetics of isoniazid affected by NAT2 polymorphisms in patients with tuberculosis: A systematic review.Clinical and translational science · 2024Pooled 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
- 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
- A Systematic Review on the Effect of HIV Infection on the Pharmacokinetics of First-Line Tuberculosis Drugs.Clinical pharmacokinetics · 2019Pooled it
- Pharmacokinetics of Rifampin, Isoniazid, Pyrazinamide, and Ethambutol in Infants Dosed According to Revised WHO-Recommended Treatment Guidelines.Antimicrobial agents and chemotherapy · 2016Trial
- Malnutrition and Its Effect on Drug Pharmacokinetics: A Clinical Perspective.Clinical pharmacokinetics · 2025Review
- Investigator-Initiated Clinical Pharmacokinetic Studies in Resource-Limited Settings: Minimal Requirements and Practical Guidance.Journal of clinical pharmacology · 2025Review
- Population pharmacokinetics of ethambutol in African children: a pooled analysis.The Journal of antimicrobial chemotherapy · 2022Article
- 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
- Tuberculosis in children with severe acute malnutrition.Expert review of respiratory medicine · 2022Review
- Effect of malnutrition on the pharmacokinetics of anti-TB drugs in Ghanaian children.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2021Article
- Population Pharmacokinetic Properties of Antituberculosis Drugs in Vietnamese Children with Tuberculous Meningitis.Antimicrobial agents and chemotherapy · 2020Article
- 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
- Revised Antituberculosis Drug Doses and Hepatotoxicity in HIV Negative Children.Indian journal of pediatrics · 2019Article
- Suboptimal Antituberculosis Drug Concentrations and Outcomes in Small and HIV-Coinfected Children in India: Recommendations for Dose Modifications.Clinical pharmacology and therapeutics · 2018Article
- Preclinical tools for the evaluation of tuberculosis treatment regimens for children.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2018Review
- Revisiting the mutant prevention concentration to guide dosing in childhood tuberculosis.The Journal of antimicrobial chemotherapy · 2017Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe available pharmacokinetic data on anti-tubercular drugs in children raises the concern of suboptimal plasma concentrations attained when doses extrapolated from adult studies are used. Also, there is lack of consensus regarding the effect of malnutrition on pharmacokinetics of anti-tubercular drugs in children. We conducted this study with the aims of determining the plasma concentrations of isoniazid, rifampicin, pyrazinamide and ethambutol achieved with different dosage of the anti-tubercular drugs so as to provide supportive evidence to the revised dosages and to evaluate the effects of malnutrition on the pharmacokinetics of these drugs in children. We also attempted to correlate the plasma concentrations of these drugs with clinical outcome of therapy.
methodProspective drug estimation study was conducted in two groups of children, age 6 months to 15 years, with tuberculosis, with or without severe malnutrition, receiving different dosage of daily anti- tubercular therapy. The dosage (range) of isoniazid was 5 (4-6) and 10 (7-15) mg/kg in the two groups, respectively, that of rifampicin-10 (8-12) and 15 (10-12) mg/kg, respectively, both the groups received same dose of pyrazinamide (30-35 mg/kg) and ethambutol (20-25 mg/kg). All four drugs were simultaneously estimated by liquid chromatography-mass spectrometry (LC-MS/MS). RESULTS AND
conclusionThe median (IQR) Cmax of isoniazid increased significantly from 0.6 (0.3,1.2) μg/mL to 3.4 (1.8, 5.0) μg/mL with increase in the dose. Plasma rifampicin concentrations increased only marginally on increasing the dose [median (IQR) Cmax: 10.4 (7.2, 13.9) μg/mL vs. 12.0 (6.1, 24.3) μg/mL, p=0.08]. For ethambutol, 55.9% of the children had inadequate 2-hour concentrations. Two-hour plasma concentrations of at least one drug were low in 59 (92.2%) and 54 (85.7%) children in the two dosing regimen, respectively. We did not observe any effect of malnutrition on pharmacokinetic parameters of the drugs studied. We did not observe an association between low plasma drug concentrations and poor outcome. We may have to be cautious while increasing the doses and strive to asses other factors influencing the drug concentrations and treatment outcomes in children.
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