The pharmacogenetics of NAT2 enzyme maturation in perinatally HIV exposed infants receiving isoniazid. Zhu, R., Kiser, J. J., Seifart, H. I., Werely, C. J., Mitchell, C. D., D'Argenio, D. Z., & Fletcher, C. V. Journal of Clinical Pharmacology, 52(4):511--519, April, 2012.
doi  abstract   bibtex   
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.
@article{ zhu_pharmacogenetics_2012,
  title = {The pharmacogenetics of {NAT}2 enzyme maturation in perinatally {HIV} exposed infants receiving isoniazid},
  volume = {52},
  issn = {1552-4604},
  doi = {10.1177/0091270011402826},
  abstract = {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.},
  language = {eng},
  number = {4},
  journal = {Journal of Clinical Pharmacology},
  author = {Zhu, Rui and Kiser, Jennifer J. and Seifart, Heiner I. and Werely, Cedric J. and Mitchell, Charles D. and D'Argenio, David Z. and Fletcher, Courtney V.},
  month = {April},
  year = {2012},
  pmid = {21558457},
  pmcid = {PMC3182303},
  keywords = {Administration, Oral, Age Factors, Antitubercular Agents, Arylamine N-Acetyltransferase, Child, Preschool, Dose-Response Relationship, Drug, Double-Blind Method, Female, Genotype, HIV Infections, Humans, Infant, Infectious Disease Transmission, Vertical, Isoniazid, Latent Tuberculosis, Male, Pharmacogenetics, Pregnancy, Pregnancy Complications, Infectious, Prospective Studies, South Africa, Tuberculosis},
  pages = {511--519}
}

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