Full-gene sequencing analysis of NAT2 and its relationship with isoniazid pharmacokinetics in Venezuelan children with tuberculosis
SourcePharmacogenomics, 15, 3, (2014), pp. 285-296
Article / Letter to editor
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Laboratory of Genetic, Endocrine and Metabolic Diseases
Paediatrics - OUD tm 2017
SubjectRadboudumc 0: Other Research RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 4: lnfectious Diseases and Global Health RIHS: Radboud Institute for Health Sciences; Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 5: Inflammatory diseases RIHS: Radboud Institute for Health Sciences
Background: Genetic variants in NAT2 are associated with pharmacokinetic variation of isoniazid, the cornerstone of antituberculosis treatment. We investigated the acetylator genotype and phenotype in children on antituberculosis treatment that were previously shown to have low plasma isoniazid levels. Materials & methods:NAT2 genotyping and phenotyping, represented as metabolic ratio of acetylisoniazid over isoniazid and as isoniazid half-life, were performed in 30 Venezuelan children. Results: Most children carried genotypes resulting in an intermediate or low enzyme activity (43 and 40%, respectively). Isoniazid exposure differed between genotypically slow and rapid acetylators (13.3 vs 4.5 hxmg/l, p < 0.01). Both the metabolic ratio as well as the half-life of isoniazid distinguished genotypically slow from genotypically rapid or intermediate acetylators (all p </= 0.01). Conclusion: In Venezuelan children a clear difference in isoniazid pharmacokinetics and acetylator phenotype between genotypically slow and genotypically intermediate or rapid acetylating children was observed. Original submitted 31 July 2013; Revision submitted 11 November 2013.
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