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|Title: ||Pharmacokinetics of First-Line Antituberculosis Drugs Using WHO Revised Dosage in ChildrenWith Tuberculosis With and Without HIV Coinfection|
|Authors: ||Kwara, Awewura|
Gillani, Fizza S.
Sarfo, Anima M.
Kwarteng Owusu, Sandra
Peloquin, Charles A.
|Keywords: ||children; first-line antituberculosis drugs|
revised WHO dosage
|Issue Date: ||2015|
|Publisher: ||Journal of the Pediatric Infectious Diseases Society|
|Citation: ||Journal of the Pediatric Infectious Diseases Society, Vol. 5, No. 4, pp. 356–65, 2016|
|Abstract: ||Pharmacokinetic data on the first-line antituberculosis drugs using the World Health
Organization (WHO) revised dosages for children are limited. We investigated the pharmacokinetics of these
drugs in children who were mostly treated with revised dosages.
Methods. Children with tuberculosis on first-line therapy for at least 4 weeks had blood samples collected at
predose, 1, 2, 4, and 8 hours postdose. Drug concentrations were determined by validated liquid
chromatography mass spectrometry methods, and pharmacokinetic parameters were calculated using
noncompartmental analysis. Factors associated with plasma peak concentration (Cmax) and the area under the
time–concentration curve 0–8 hours (AUC0–8h) of each drug was examined using univariate and multivariate
Results. Of the 62 children, 32 (51.6%)were male, 29 (46.8%) were younger than 5 years old, and 28 (45.2%)
had human immunodeficiency virus (HIV) coinfection. Three patients had undetectable pyrazinamide and
ethambutol concentrations. The median (interquartile range) AUC0–8h for isoniazid was 17.7 (10.2–23.4) μg·h
mL–1, rifampin was 26.0 (15.3–36.1) μg·h mL–1, pyrazinamide was 144.6 (111.5–201.2) μg·h mL–1, and
ethambutol was 6.7 (3.8–10.4) μg·h mL–1. Of the children who received recommended weight-band dosages,
44/51 (86.3%), 46/56 (82.1%), 27/56 (48.2%), and 21/51 (41.2%) achieved target Cmax for isoniazid,
pyrazinamide, ethambutol, and rifampin, respectively. In multivariate analysis, age, sex, HIV coinfection status,
and drug dosage in milligrams per kilogram were associated with the drugs’ plasma drug Cmax or AUC0–8h.
Conclusions. The revised dosages appeared to be adequate for isoniazid and pyrazinamide, but not for
rifampin or ethambutol in this population. Higher dosages of rifampin and ethambutol than currently
recommended may be required in most children.|
|Description: ||This article is published in Journal of the Pediatric Infectious Diseases Society,and also available at DOI:10.1093/jpids/piv035|
|Appears in Collections:||College of Health Sciences|
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