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Free Content Age, nutritional status and INH acetylator status affect pharmacokinetics of anti-tuberculosis drugs in children

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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.

Keywords: children; intermittent, therapeutic drug monitoring; pharmacokinetics; rifampicin; tuberculosis

Document Type: Research Article


Affiliations: 1: National Institute for Research in Tuberculosis, Indian Council of Medical Research, Chetpet, Chennai, India 2: Institute of Child Health, Chennai, India 3: Government Hospital of Thoracic Medicine, Chennai, India 4: Government Rajaji Hospital, Madurai, India

Publication date: 2013-06-01

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

    Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website

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