Population screening for isoniazid acetylator phenotype
| Autor: | D. P. Parkin, B. J. Van Der Walt, H. I. Seifart, Peter R. Donald, F J Botha |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
Male Tuberculosis Genotype Epidemiology Metabolite Antitubercular Agents Biological Availability Pharmacology chemistry.chemical_compound Polymorphism (computer science) Isoniazid medicine Humans Distribution (pharmacology) Pharmacology (medical) Tuberculosis Pulmonary Chromatography High Pressure Liquid Polymorphism Genetic Arylamine N-acetyltransferase medicine.diagnostic_test business.industry Acetylation bacterial infections and mycoses medicine.disease Bioavailability Phenotype chemistry Therapeutic drug monitoring Area Under Curve Female Drug Monitoring business medicine.drug |
| Zdroj: | Pharmacoepidemiology and Drug Safety. 10:127-134 |
| ISSN: | 1099-1557 1053-8569 |
| DOI: | 10.1002/pds.570 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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