Document Detail


The Pharmacogenetics of NAT2 Enzyme Maturation in Perinatally HIV Exposed Infants Receiving Isoniazid.
MedLine Citation:
PMID:  21558457     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Rui Zhu; Jennifer J Kiser; Heiner I Seifart; Cedric J Werely; Charles D Mitchell; David Z D'Argenio; Courtney V Fletcher
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-10
Journal Detail:
Title:  Journal of clinical pharmacology     Volume:  -     ISSN:  1552-4604     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0366372     Medline TA:  J Clin Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
University of Southern California.
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