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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): University of Southern California.

Publication date & source: 2011-05-10, J Clin Pharmacol., [Epub ahead of print]

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.

Page last updated: 2011-12-09

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