The pharmacogenetics of NAT2 enzyme maturation in perinatally HIV exposed infants
receiving isoniazid.
Author(s): Zhu R, Kiser JJ, Seifart HI, Werely CJ, Mitchell CD, D'Argenio DZ, Fletcher CV.
Affiliation(s): Biomedical Simulations Resource (BMSR), University of Southern California, Los
Angeles, CA 90089, USA.
Publication date & source: 2012, J Clin Pharmacol. , 52(4):511-9
The roles of the NAT2 genotype and enzyme maturation on isoniazid
pharmacokinetics were investigated in South African infants with perinatal HIV
exposure enrolled in a randomized, double-blind, controlled trial of isoniazid
for prevention of tuberculosis disease and latent infection. Plasma
concentration-time measurements of isoniazid from 151 infants (starting at 3-4
months of age) receiving isoniazid 10 to 20 mg/kg/d orally during the course of
the 24-month study were incorporated in a population analysis along with NAT2
genotype, body weight, age, and sex. The results showed a different NAT2 enzyme
maturation profile for each of the 3 acetylation groups, with the 70-kg body
weight-normalized typical apparent clearance for the fast and intermediate
acetylators increasing from 14.25 L/h and 10.88 L/h at 3 months of age to 22.84
L/h and 15.58 L/h at 24 months of age, respectively, with no significant change
in the apparent clearance of the slow group during this period. A hypothesis is
proposed to explain the genotype-dependent enzyme maturation processes for the
NAT2 enzyme.
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