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 metabolite, acetyl-isoniazid, were determined by HPLC analyses at various postdose 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 (C) 2001 John Wiley & Sons, Ltd.