Pharmacokinetics of anti-tuberculosis drugs in Venezuelan children younger than 16 years of age: supportive evidence for the implementation of revised WHO dosing recommendations.
Trop Med Int Health
; 17(12): 1449-56, 2012 Dec.
Article
em En
| MEDLINE
| ID: mdl-23094704
ABSTRACT
OBJECTIVES:
The World Health Organization (WHO) recently issued revised first-line antituberculosis (anti-TB) drug dose recommendations for children, with dose increases proposed for each drug. No pharmacokinetic data are available from South American children. We examined the need for implementation of these revised guidelines in Venezuela.METHODS:
Plasma isoniazid, rifampicin, pyrazinamide and ethambutol concentrations were assessed prior to and at 2, 4 and 8 h after intake of TB drugs by 30 TB patients aged 1-15 years. The effects of dose in mg/kg, age, sex, body weight, malnutrition and acetylator phenotype on maximum plasma drug concentrations (Cmax) and exposure (AUC0-24) were determined.RESULTS:
25 patients (83%) had an isoniazid Cmax below 3 mg/l and 23 patients (77%) had a rifampicin Cmax below 8 mg/l. One patient (3%) had a pyrazinamide Cmax below 20 mg/l. The low number of patients on ethambutol (n = 5) precluded firm conclusions. Cmax and AUC0-24 of all four drugs were significantly and positively correlated with age and body weight. Patients aged 1-4 years had significantly lower Cmax and AUC0-24 values for isoniazid and rifampicin and a trend to lower values for pyrazinamide compared to those aged 5-15 years. The geometric mean AUC0-24 for isoniazid was much lower in fast acetylators than in slow acetylators (5.2 vs. 12.0, P < 0.01).CONCLUSION:
We provide supportive evidence for the implementation of the revised WHO pediatric TB drug dose recommendations in Venezuela. Follow-up studies are needed to describe the corresponding plasma levels that are achieved by the recommended increased doses of TB drugs.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tuberculose
/
Guias de Prática Clínica como Assunto
/
Antituberculosos
Tipo de estudo:
Guideline
/
Observational_studies
/
Prognostic_studies
Limite:
Adolescent
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
País/Região como assunto:
America do sul
/
Venezuela
Idioma:
En
Revista:
Trop Med Int Health
Assunto da revista:
MEDICINA TROPICAL
/
SAUDE PUBLICA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Holanda