Isoniazid pharmacokinetics in children treated for respiratory tuberculosis
dc.contributor.author | Schaaf H.S. | |
dc.contributor.author | Parkin D.P. | |
dc.contributor.author | Seifart H.I. | |
dc.contributor.author | Werely C.J. | |
dc.contributor.author | Hesseling P.B. | |
dc.contributor.author | Van Helden P.D. | |
dc.contributor.author | Maritz J.S. | |
dc.contributor.author | Donald P.R. | |
dc.date.accessioned | 2011-05-15T16:15:37Z | |
dc.date.available | 2011-05-15T16:15:37Z | |
dc.date.issued | 2005 | |
dc.description.abstract | Aims: 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.version | Article | |
dc.identifier.citation | Archives of Disease in Childhood | |
dc.identifier.citation | 90 | |
dc.identifier.citation | 6 | |
dc.identifier.issn | 00039888 | |
dc.identifier.other | 10.1136/adc.2004.052175 | |
dc.identifier.uri | http://hdl.handle.net/10019.1/13417 | |
dc.subject | acyltransferase | |
dc.subject | isoniazid | |
dc.subject | acetylator phenotype | |
dc.subject | adolescent | |
dc.subject | adult | |
dc.subject | age | |
dc.subject | area under the curve | |
dc.subject | article | |
dc.subject | body weight | |
dc.subject | child | |
dc.subject | dose calculation | |
dc.subject | drug blood level | |
dc.subject | drug elimination | |
dc.subject | ethnology | |
dc.subject | genotype | |
dc.subject | heterozygosity | |
dc.subject | homozygosity | |
dc.subject | human | |
dc.subject | infant | |
dc.subject | lung tuberculosis | |
dc.subject | major clinical study | |
dc.subject | nucleotide sequence | |
dc.subject | pharmacogenetics | |
dc.subject | priority journal | |
dc.subject | regression analysis | |
dc.subject | Adolescent | |
dc.subject | Adult | |
dc.subject | Aging | |
dc.subject | Analysis of Variance | |
dc.subject | Antitubercular Agents | |
dc.subject | Area Under Curve | |
dc.subject | Arylamine N-Acetyltransferase | |
dc.subject | Child | |
dc.subject | Child, Preschool | |
dc.subject | Genotype | |
dc.subject | Heterozygote | |
dc.subject | Homozygote | |
dc.subject | Humans | |
dc.subject | Infant | |
dc.subject | Infant, Newborn | |
dc.subject | Isoniazid | |
dc.subject | Tuberculosis, Pulmonary | |
dc.title | Isoniazid pharmacokinetics in children treated for respiratory tuberculosis | |
dc.type | Article |