title: Population screening for isoniazid acetylator phenotype.
abstract: OBJECTIVE
  To establish a useful method for acetylator phenotypification and therapeutic drug monitoring of patients receiving isoniazid.
  
  
  METHODS
  Sixty patients with uncomplicated pulmonary tuberculosis were given a 5-mg/kg oral dose of isoniazid each. Plasma concentrations of isoniazid and its metabolite, acetyl-isoniazid, were determined by HPLC analyses at various post-dose times. From the isoniazid concentration and the concentration ratio of acetyl-isoniazid and isoniazid (metabolic ratio), phenotypification methods were assessed.
  
  
  RESULTS
  The metabolic ratios at 3 h post-dose revealed a trimodal distribution; a fast, intermediate and slow acetylator phenotype group. The 2-h and 6-h data showed different bimodal combinations of these phenotype groups. The metabolic ratio phenotypification method could be simplified by using the HPLC data directly without converting it to absolute concentrations.
  
  
  CONCLUSIONS
  A single-sample test based upon the plasma isoniazid concentration, combined with the metabolic ratio of acetyl-isoniazid and isoniazid, appears to be a reliable parameter for phenotype discrimination and for bioavailability testing.
authors.affiliation: Department of Pharmacology, University of Stellenbosch, Republic of South Africa.
authors.forename: H I
authors.initials: HI
authors.lastname: Seifart
authors.forename: D P
authors.initials: DP
authors.lastname: Parkin
authors.forename: F J
authors.initials: FJ
authors.lastname: Botha
authors.forename: P R
authors.initials: PR
authors.lastname: Donald
authors.forename: B J
authors.initials: BJ
authors.lastname: Van Der Walt
mesh_terms: D000107:Acetylation; D000328:Adult; D000995:Antitubercular Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring; D005260:Female; D005838:Genotype; D006801:Humans; D007538:Isoniazid / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid