Isoniazid pharmacokinetics in children treated for respiratory tuberculosis

Schaaf H.S.
Parkin D.P.
Seifart H.I.
Werely C.J.
Hesseling P.B.
Van Helden P.D.
Maritz J.S.
Donald P.R.

Open link

Publication date

January 2005

DOI

10.1136/adc.2004.052175

Publisher

BMJ

ISSN

0003-9888

Citation count (estimate)

102

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 regressi...