Isoniazid pharmacokinetics in children treated for respiratory tuberculosis

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dc.contributor.authorSchaaf H.S.
dc.contributor.authorParkin D.P.
dc.contributor.authorSeifart H.I.
dc.contributor.authorWerely C.J.
dc.contributor.authorHesseling P.B.
dc.contributor.authorVan Helden P.D.
dc.contributor.authorMaritz J.S.
dc.contributor.authorDonald P.R.
dc.date.accessioned2011-05-15T16:15:37Z
dc.date.available2011-05-15T16:15:37Z
dc.date.issued2005
dc.description.abstractAims: To define the pharmacokinetics of isoniazid (INH) in children with tuberculosis in relation to the N-acetyltransferase 2 (NAT2) genotype. Methods: The first order elimination rate constant (k) and area under the concentration curve (AUC) were calculated in 64 children <13 years of age (median 3.8) with respiratory tuberculosis from INH concentrations determined 2-5 hours after a 10 mg/kg INH dose. The NAT2 genotype was determined; 25 children were classified as homozygous slow (SS), 24 as heterozygous fast (FS), and 15 as homozygous fast (FF) acetylators. Results: The mean (SD) k values of the genotypes differed significantly from one another: SS 0.254 (0.046), FS 0.513 (0.074), FF 0.653 (0.117). Within each genotype a median regression of k on age showed a significant decrease in k with age. The mean (SD) INH concentrations (mg/l) two hours after INH administration were SS 8.599 (1.974), FS 5.131 (1.864), and FF 3.938 (1.754). A within genotype regression of 2-hour INH concentrations on age showed a significant increase with age. A within genotype regression of 3-hour, 4-hour, and 5-hour concentrations on age also showed a significant increase with age in each instance. In ethnically similar adults, mean (SD) 2-hour INH concentrations (mg/l) for each genotype were significantly higher than the children's: SS 10.942 (1.740), FS 8.702 (1.841), and FF 6.031 (1.431). Conclusions: Younger children eliminate INH faster than older children and, as a group, faster than adults, and require a higher mg/kg body weight INH dose to achieve serum concentrations comparable to adults.
dc.description.versionArticle
dc.identifier.citationArchives of Disease in Childhood
dc.identifier.citation90
dc.identifier.citation6
dc.identifier.issn00039888
dc.identifier.other10.1136/adc.2004.052175
dc.identifier.urihttp://hdl.handle.net/10019.1/13417
dc.subjectacyltransferase
dc.subjectisoniazid
dc.subjectacetylator phenotype
dc.subjectadolescent
dc.subjectadult
dc.subjectage
dc.subjectarea under the curve
dc.subjectarticle
dc.subjectbody weight
dc.subjectchild
dc.subjectdose calculation
dc.subjectdrug blood level
dc.subjectdrug elimination
dc.subjectethnology
dc.subjectgenotype
dc.subjectheterozygosity
dc.subjecthomozygosity
dc.subjecthuman
dc.subjectinfant
dc.subjectlung tuberculosis
dc.subjectmajor clinical study
dc.subjectnucleotide sequence
dc.subjectpharmacogenetics
dc.subjectpriority journal
dc.subjectregression analysis
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAging
dc.subjectAnalysis of Variance
dc.subjectAntitubercular Agents
dc.subjectArea Under Curve
dc.subjectArylamine N-Acetyltransferase
dc.subjectChild
dc.subjectChild, Preschool
dc.subjectGenotype
dc.subjectHeterozygote
dc.subjectHomozygote
dc.subjectHumans
dc.subjectInfant
dc.subjectInfant, Newborn
dc.subjectIsoniazid
dc.subjectTuberculosis, Pulmonary
dc.titleIsoniazid pharmacokinetics in children treated for respiratory tuberculosis
dc.typeArticle
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