Document Detail


The pharmacogenetics of NAT2 enzyme maturation in perinatally HIV exposed infants receiving isoniazid.
MedLine Citation:
PMID:  21558457     Owner:  NLM     Status:  MEDLINE    
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:  Clinical Trial, Phase II; Clinical Trial, Phase III; Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural     Date:  2011-05-10
Journal Detail:
Title:  Journal of clinical pharmacology     Volume:  52     ISSN:  1552-4604     ISO Abbreviation:  J Clin Pharmacol     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-28     Completed Date:  2012-07-27     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  0366372     Medline TA:  J Clin Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  511-9     Citation Subset:  IM    
Affiliation:
Biomedical Simulations Resource (BMSR), University of Southern California, Los Angeles, CA 90089, USA.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Age Factors
Antitubercular Agents / administration & dosage,  pharmacokinetics*,  therapeutic use
Arylamine N-Acetyltransferase / genetics*
Child, Preschool
Dose-Response Relationship, Drug
Double-Blind Method
Female
Genotype
HIV Infections / transmission
Humans
Infant
Infectious Disease Transmission, Vertical
Isoniazid / administration & dosage,  pharmacokinetics*,  therapeutic use*
Latent Tuberculosis / prevention & control
Male
Pharmacogenetics
Pregnancy
Pregnancy Complications, Infectious / epidemiology
Prospective Studies
South Africa
Tuberculosis / prevention & control
Grant Support
ID/Acronym/Agency:
N01-DK-9-001/DK/NIDDK NIH HHS; P41 EB001978-26/EB/NIBIB NIH HHS; P41 EB001978-27/EB/NIBIB NIH HHS; U01 AI068632/AI/NIAID NIH HHS; U01 AI068632-04/AI/NIAID NIH HHS; UO1-AI068632/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antitubercular Agents; 54-85-3/Isoniazid; EC 2.3.1.5/Arylamine N-Acetyltransferase; EC 2.3.1.5/NAT2 protein, human
Comments/Corrections

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