Population screening for isoniazid acetylator phenotype

Purpose 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 metabol...

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Published in:Pharmacoepidemiology and drug safety 2001-03, Vol.10 (2), p.127-134
Main Authors: Seifart, Heiner I., Parkin, Donald P., Botha, Frederik J. H., Donald, Peter R., Van Der Walt, Ben J.
Format: Article
Language:English
Subjects:
Acetylation
Adult
Antitubercular Agents - blood
Antitubercular Agents - pharmacokinetics
Antitubercular Agents - therapeutic use
Area Under Curve
arylamine N-acetyltransferase
bioavailability
Biological Availability
Chromatography, High Pressure Liquid
Drug Monitoring
efficacy
Female
Genotype
Humans
isoniazid
Isoniazid - blood
Isoniazid - pharmacokinetics
Isoniazid - therapeutic use
Male
Phenotype
polymorphism
Polymorphism, Genetic
trimodality
Tuberculosis, Pulmonary - drug therapy
Tuberculosis, Pulmonary - metabolism
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Summary:Purpose 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. Copyright © 2001 John Wiley & Sons, Ltd.
ISSN:1053-8569
1099-1557
DOI:10.1002/pds.570