Trial reportAntimicrobial agents and chemotherapy2015
Pharmacokinetics of first-line antituberculosis drugs in HIV-infected children with tuberculosis treated with intermittent regimens in India.
Trial report in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 3 of them syntheses that pooled it.
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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
21 citing papers in PubMed, 3 syntheses or guidelines pooled 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 the First-Line Antituberculosis Drugs in Ghanaian Children with Tuberculosis with or without HIV Coinfection.Antimicrobial agents and chemotherapy · 2017Trial
- Pharmacokinetics of Rifampin, Isoniazid, Pyrazinamide, and Ethambutol in Infants Dosed According to Revised WHO-Recommended Treatment Guidelines.Antimicrobial agents and chemotherapy · 2016Trial
- Analysis of factors influencing plasma concentrations of anti-TB drugs in pediatric TB patients.BMC infectious diseases · 2025Article
- Investigation on the in vitro anti-Trichophyton activity of photosensitizers.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2022Article
- Article
- Pharmacokinetics of First-Line Drugs Among Children With Tuberculosis in Rural Tanzania.Journal of the Pediatric Infectious Diseases Society · 2020Article
- Clinical Significance of the Plasma Protein Binding of Rifampicin in the Treatment of Tuberculosis Patients.Clinical pharmacokinetics · 2019Article
- Safety and efficacy of rifabutin among HIV/TB-coinfected children on lopinavir/ritonavir-based ART.The Journal of antimicrobial chemotherapy · 2019Article
- Alternative dosing guidelines to improve outcomes in childhood tuberculosis: a mathematical modelling study.The Lancet. Child & adolescent health · 2019Article
- Tuberculosis notification in a private tertiary care teaching hospital in South India: a mixed-methods study.BMJ open · 2019Article
- Suboptimal Antituberculosis Drug Concentrations and Outcomes in Small and HIV-Coinfected Children in India: Recommendations for Dose Modifications.Clinical pharmacology and therapeutics · 2018Article
- 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.The Pediatric infectious disease journal · 2018Observational
- Revisiting the mutant prevention concentration to guide dosing in childhood tuberculosis.The Journal of antimicrobial chemotherapy · 2017Review
- Isoniazid concentrations in hair and plasma area-under-the-curve exposure among children with tuberculosis.PloS one · 2017Article
- Pharmacokinetics of First-Line Antituberculosis Drugs Using WHO Revised Dosage in Children With Tuberculosis With and Without HIV Coinfection.Journal of the Pediatric Infectious Diseases Society · 2016Observational
- Drug Concentration Thresholds Predictive of Therapy Failure and Death in Children With Tuberculosis: Bread Crumb Trails in Random Forests.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2016Article
- A Long-term Co-perfused Disseminated Tuberculosis-3D Liver Hollow Fiber Model for Both Drug Efficacy and Hepatotoxicity in Babies.EBioMedicine · 2016Article
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The objective of this report was to study the pharmacokinetics of rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA) in HIV-infected children with tuberculosis (TB) treated with a thrice-weekly anti-TB regimen in the government program in India. Seventy-seven HIV-infected children with TB aged 1 to 15 years from six hospitals in India were recruited. During the intensive phase of TB treatment with directly observed administration of the drugs, a complete pharmacokinetic study was performed. Drug concentrations were measured by high-performance liquid chromatography. A multivariable regression analysis was done to explore the factors impacting drug levels and treatment outcomes. The proportions of children with subnormal peak concentrations (Cmax) of RMP, INH, and PZA were 97%, 28%, and 33%, respectively. Children less than 5 years old had a lower median Cmax and lower exposure (area under the time-concentration curve from 0 to 8 h [AUC0-8]) of INH (Cmax, 2.5 versus 5.1 μg/ml, respectively [P=0.016]; AUC0-8, 11.1 versus 22.0 μg/ml·h, respectively [P=0.047[) and PZA (Cmax, 34.1 versus 42.3 μg/ml, respectively [P=0.055]; AUC0-8, 177.9 versus 221.7 μg/ml·h, respectively [P=0.05]) than those more than 5 years old. In children with unfavorable versus favorable outcomes, the median Cmax of RMP (1.0 versus 2.8 μg/ml, respectively; P=0.002) and PZA (31.9 versus 44.4 μg/ml, respectively; P=0.045) were significantly lower. Among all factors studied, the PZA Cmax influenced TB treatment outcome (P=0.011; adjusted odds ratio, 1.094; 95% confidence interval, 1.021 to 1.173). A high proportion of children with HIV and TB had a subnormal RMP Cmax. The PZA Cmax significantly influenced treatment outcome. These findings have important clinical implications and emphasize that drug doses in HIV-infected children with TB have to be optimized.
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