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Farmacocinética de medicamentos antituberculosos en niños Venezolanos menores de 16 años: evidencia que apoya la implementación de las recomendaciones revisadas de la OMS sobre la dosificación
Author(s) -
Verhagen L. M.,
López D.,
Hermans P. W. M.,
Warris A.,
de Groot R.,
García J. F.,
de Waard J. H.,
Aarnoutse R. E.
Publication year - 2012
Publication title -
tropical medicine and international health
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.056
H-Index - 114
eISSN - 1365-3156
pISSN - 1360-2276
DOI - 10.1111/tmi.12003
Subject(s) - pyrazinamide , ethambutol , rifampicin , isoniazid , medicine , pharmacokinetics , dosing , tuberculosis , drug , pharmacology , pediatrics , gastroenterology , pathology
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 (C max ) and exposure (AUC 0‐24 ) were determined. Results 25 patients (83%) had an isoniazid C max below 3 mg/l and 23 patients (77%) had a rifampicin C max below 8 mg/l. One patient (3%) had a pyrazinamide C max below 20 mg/l. The low number of patients on ethambutol ( n = 5) precluded firm conclusions. C max and AUC 0‐24 of all four drugs were significantly and positively correlated with age and body weight. Patients aged 1–4 years had significantly lower C max and AUC 0‐24 values for isoniazid and rifampicin and a trend to lower values for pyrazinamide compared to those aged 5–15 years. The geometric mean AUC 0‐24 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.