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Age, nutritional status and INH acetylator status affect pharmacokinetics of anti-tuberculosis drugs in children.
Ramachandran, G; Hemanth Kumar, A K; Bhavani, P K; Poorana Gangadevi, N; Sekar, L; Vijayasekaran, D; Banu Rekha, V V; Ramesh Kumar, S; Ravichandran, N; Mathevan, G; Swaminathan, S.
Afiliación
  • Ramachandran G; National Institute for Research in Tuberculosis, Indian Council of Medical Research, Chetpet, Chennai, India.
Int J Tuberc Lung Dis ; 17(6): 800-6, 2013 Jun.
Article en En | MEDLINE | ID: mdl-23676165
SETTING: The currently recommended dosages of rifampicin (RMP), isoniazid (INH), pyrazinamide (PZA) and ethambutol in children are extrapolated from adult pharmacokinetic studies, and have not been adequately evaluated in children. OBJECTIVE: To describe the pharmacokinetics of RMP, INH and PZA given thrice weekly in children with tuberculosis (TB), and to relate pharmacokinetics to treatment outcomes. METHODS: Eighty-four human immunodeficiency virus negative children with TB aged 1-12 years in Chennai and Madurai, India, were recruited. Phenotypic INH acetylator status was determined. Nutritional status was assessed using Z scores. During the intensive phase of anti-tuberculosis treatment, a complete pharmacokinetic study was performed after directly observed administration of drugs. At 2 and 6 months, drug levels were measured 2 h post-dose. Drug concentrations were measured using high performance liquid chromatography and pharmacokinetic variables were calculated. Multivariable regression analysis was performed to explore factors impacting drug levels and treatment outcomes. RESULTS AND CONCLUSIONS: Children aged <3 years had significantly lower RMP, INH and PZA concentrations than older children, and 90% of all children had sub-therapeutic RMP Cmax (<8 µg/ml). Age, nutritional status and INH acetylator status influenced drug levels. Peak RMP and INH concentrations were important determinants of treatment outcome. Recommendations for anti-tuberculosis treatment in children should take these factors into consideration.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirazinamida / Rifampin / Isoniazida / Antituberculosos Tipo de estudio: Diagnostic_studies / Guideline / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Child / Child, preschool / Female / Humans / Infant / Male País/Región como asunto: Asia Idioma: En Revista: Int J Tuberc Lung Dis Año: 2013 Tipo del documento: Article País de afiliación: India Pais de publicación: Francia
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirazinamida / Rifampin / Isoniazida / Antituberculosos Tipo de estudio: Diagnostic_studies / Guideline / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Child / Child, preschool / Female / Humans / Infant / Male País/Región como asunto: Asia Idioma: En Revista: Int J Tuberc Lung Dis Año: 2013 Tipo del documento: Article País de afiliación: India Pais de publicación: Francia