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Age, nutritional status and INH acetylator status affect pharmacokinetics of anti-tuberculosis drugs in children.
Int J Tuberc Lung Dis. 2013 Jun; 17(6):800-6.IJ

Abstract

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.

Authors+Show Affiliations

National Institute for Research in Tuberculosis, Indian Council of Medical Research, Chetpet, Chennai, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23676165

Citation

Ramachandran, G, et al. "Age, Nutritional Status and INH Acetylator Status Affect Pharmacokinetics of Anti-tuberculosis Drugs in Children." The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease, vol. 17, no. 6, 2013, pp. 800-6.
Ramachandran G, Hemanth Kumar AK, Bhavani PK, et al. Age, nutritional status and INH acetylator status affect pharmacokinetics of anti-tuberculosis drugs in children. Int J Tuberc Lung Dis. 2013;17(6):800-6.
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. (2013). Age, nutritional status and INH acetylator status affect pharmacokinetics of anti-tuberculosis drugs in children. The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease, 17(6), 800-6. https://doi.org/10.5588/ijtld.12.0628
Ramachandran G, et al. Age, Nutritional Status and INH Acetylator Status Affect Pharmacokinetics of Anti-tuberculosis Drugs in Children. Int J Tuberc Lung Dis. 2013;17(6):800-6. PubMed PMID: 23676165.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Age, nutritional status and INH acetylator status affect pharmacokinetics of anti-tuberculosis drugs in children. AU - Ramachandran,G, AU - Hemanth Kumar,A K, AU - Bhavani,P K, AU - Poorana Gangadevi,N, AU - Sekar,L, AU - Vijayasekaran,D, AU - Banu Rekha,V V, AU - Ramesh Kumar,S, AU - Ravichandran,N, AU - Mathevan,G, AU - Swaminathan,S, PY - 2013/5/17/entrez PY - 2013/5/17/pubmed PY - 2013/12/16/medline SP - 800 EP - 6 JF - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease JO - Int. J. Tuberc. Lung Dis. VL - 17 IS - 6 N2 - 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. SN - 1815-7920 UR - https://www.unboundmedicine.com/medline/citation/23676165/Age_nutritional_status_and_INH_acetylator_status_affect_pharmacokinetics_of_anti_tuberculosis_drugs_in_children_ L2 - https://www.ingentaconnect.com/openurl?genre=article&amp;issn=1027-3719&amp;volume=17&amp;issue=6&amp;spage=800&amp;aulast=Ramachandran DB - PRIME DP - Unbound Medicine ER -