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.
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.
Authors: Scott K Heysell; Charles Mtabho; Stellah Mpagama; Solomon Mwaigwisya; Suporn Pholwat; Norah Ndusilo; Jean Gratz; Rob E Aarnoutse; Gibson S Kibiki; Eric R Houpt Journal: Antimicrob Agents Chemother Date: 2011-10-03 Impact factor: 5.191
Authors: Alma Tostmann; Charles M Mtabho; Hadija H Semvua; Jossy van den Boogaard; Gibson S Kibiki; Martin J Boeree; Rob E Aarnoutse Journal: Antimicrob Agents Chemother Date: 2013-04-29 Impact factor: 5.191
Authors: Jong Sun Park; Jae-Yeon Lee; Yeon Joo Lee; Se Joong Kim; Young-Jae Cho; Ho Il Yoon; Choon-Taek Lee; Junghan Song; Jae Ho Lee Journal: Antimicrob Agents Chemother Date: 2015-10-12 Impact factor: 5.191
Authors: Monadil H Ali; Alian A Alrasheedy; Dan Kibuule; Mohamed Azmi Hassali; Brian Godman; Mohammed F Abdelwahab; Raef Y Abbadi Journal: J Clin Tuberc Other Mycobact Dis Date: 2019-09-06