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System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis
09:57

System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis

Published on: April 5, 2017

Isoniazid pharmacokinetics in children treated for respiratory tuberculosis

H S Schaaf1, D P Parkin, H I Seifart

  • 1Department of Paediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, Tygerberg Children's Hospital, South Africa. hss@sun.ac.za

Archives of Disease in Childhood
|May 24, 2005
PubMed

Insights

Children with tuberculosis eliminate isoniazid (INH) faster than adults, with younger children showing quicker clearance. This suggests a need for higher INH doses in pediatric patients to achieve therapeutic levels.

Area of Science:

  • Pharmacokinetics and Pharmacogenomics
  • Pediatric Tuberculosis Treatment
  • Drug Metabolism

Background:

  • Isoniazid (INH) is a primary drug for tuberculosis treatment.
  • Individual variability in INH pharmacokinetics can affect treatment efficacy.
  • The N-acetyltransferase 2 (NAT2) genotype influences INH metabolism.

Purpose of the Study:

  • To determine the pharmacokinetic profile of isoniazid (INH) in children with tuberculosis.
  • To investigate the relationship between INH pharmacokinetics and the N-acetyltransferase 2 (NAT2) genotype in pediatric patients.

Main Methods:

  • Calculated elimination rate constant (k) and area under the concentration curve (AUC) in 64 children (<13 years) with respiratory tuberculosis.
  • Determined INH concentrations 2-5 hours post-dose (10 mg/kg).
  • Classified children into NAT2 genotypes: homozygous slow (SS), heterozygous fast (FS), and homozygous fast (FF) acetylators.

Main Results:

  • Significant differences in mean k values observed across NAT2 genotypes (SS, FS, FF).
  • Elimination rate (k) decreased with age within each genotype.
  • Children exhibited lower INH concentrations compared to ethnically similar adults across all genotypes.

Conclusions:

  • Younger children eliminate INH more rapidly than older children and adults.
  • Pediatric patients may require higher INH doses per kilogram of body weight to reach adult-level serum concentrations.
  • NAT2 genotype significantly impacts INH elimination in children.
Abstract

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