Pharmacokinetics of First-Line Drugs Among Children With Tuberculosis in Rural Tanzania.
Adolescent
Antitubercular Agents
/ administration & dosage
Child
Child, Preschool
Drug Therapy, Combination
Ethambutol
/ administration & dosage
Female
HIV Seronegativity
Humans
Infant
Isoniazid
/ administration & dosage
Longitudinal Studies
Male
Mycobacterium tuberculosis
Pyrazinamide
/ administration & dosage
Rifampin
/ administration & dosage
Rural Population
Tanzania
Tuberculosis
/ blood
East Africa
malnutrition
pediatric
pharmacokinetics
tuberculosis
Journal
Journal of the Pediatric Infectious Diseases Society
ISSN: 2048-7207
Titre abrégé: J Pediatric Infect Dis Soc
Pays: England
ID NLM: 101586049
Informations de publication
Date de publication:
28 Feb 2020
28 Feb 2020
Historique:
received:
03
05
2018
accepted:
17
10
2018
pubmed:
6
11
2018
medline:
1
7
2020
entrez:
6
11
2018
Statut:
ppublish
Résumé
Dosing recommendations for treating childhood tuberculosis (TB) were revised by the World Health Organization, yet so far, pharmacokinetic studies that have evaluated these changes are relatively limited. We evaluated plasma drug concentrations of rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA), and ethambutol (EMB) among children undergoing TB treatment in Tanzania when these dosing recommendations were being implemented. At the end of intensive-phase TB therapy, blood was obtained 2 hours after witnessed medication administration to estimate the peak drug concentration (C2h), measured using high-performance liquid chromatography or liquid chromatography-tandem mass spectrometry methods. Differences in median drug concentrations were compared on the basis of the weight-based dosing strategy using the Mann-Whitney U test. Risk factors for low drug concentrations were analyzed using multivariate regression analysis. We enrolled 51 human immunodeficiency virus-negative children (median age, 5.3 years [range, 0.75-14 years]). The median C2hs were below the target range for each TB drug studied. Compared with children who received the "old" dosages, those who received the "revised" WHO dosages had a higher median C2h for RIF (P = .049) and PZA (P = .015) but not for INH (P = .624) or EMB (P = .143); however, these revised dosages did not result in the target range for RIF, INH, and EMB being achieved. A low starting dose was associated with a low C2h for RIF (P = .005) and PZA (P = .005). Malnutrition was associated with a low C2h for RIF (P = .001) and INH (P = .001). Among this cohort of human immunodeficiency virus-negative Tanzanian children, use of the revised dosing strategy for treating childhood TB did not result in the target drug concentration for RIF, INH, or EMB being reached.
Sections du résumé
BACKGROUND
BACKGROUND
Dosing recommendations for treating childhood tuberculosis (TB) were revised by the World Health Organization, yet so far, pharmacokinetic studies that have evaluated these changes are relatively limited. We evaluated plasma drug concentrations of rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA), and ethambutol (EMB) among children undergoing TB treatment in Tanzania when these dosing recommendations were being implemented.
METHODS
METHODS
At the end of intensive-phase TB therapy, blood was obtained 2 hours after witnessed medication administration to estimate the peak drug concentration (C2h), measured using high-performance liquid chromatography or liquid chromatography-tandem mass spectrometry methods. Differences in median drug concentrations were compared on the basis of the weight-based dosing strategy using the Mann-Whitney U test. Risk factors for low drug concentrations were analyzed using multivariate regression analysis.
RESULTS
RESULTS
We enrolled 51 human immunodeficiency virus-negative children (median age, 5.3 years [range, 0.75-14 years]). The median C2hs were below the target range for each TB drug studied. Compared with children who received the "old" dosages, those who received the "revised" WHO dosages had a higher median C2h for RIF (P = .049) and PZA (P = .015) but not for INH (P = .624) or EMB (P = .143); however, these revised dosages did not result in the target range for RIF, INH, and EMB being achieved. A low starting dose was associated with a low C2h for RIF (P = .005) and PZA (P = .005). Malnutrition was associated with a low C2h for RIF (P = .001) and INH (P = .001).
CONCLUSIONS
CONCLUSIONS
Among this cohort of human immunodeficiency virus-negative Tanzanian children, use of the revised dosing strategy for treating childhood TB did not result in the target drug concentration for RIF, INH, or EMB being reached.
Identifiants
pubmed: 30395239
pii: 5161228
doi: 10.1093/jpids/piy106
pmc: PMC7317157
doi:
Substances chimiques
Antitubercular Agents
0
Pyrazinamide
2KNI5N06TI
Ethambutol
8G167061QZ
Isoniazid
V83O1VOZ8L
Rifampin
VJT6J7R4TR
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
14-20Subventions
Organisme : NIAID NIH HHS
ID : U01 AI115594
Pays : United States
Informations de copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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