Isoniazid Acetylation Phenotyping in the Japanese: The Molar Metabolic Ratio INH/AcINH

The N-acetylation phenotyping of isoniazid (INH) was studied in 434 unrelated Japanese pulmonary tuberculosis patients. The frequency of slow acetylators was determined using three methods based on the urinary levels of INH and AcINH: percentage acetylisoniazid (%AcINH), the inactivation index or acetylation index (AcINH/INH), and the molar metabolic ratio (INH/AcINH) in urine. Frequency histograms and probit plots were constructed with the data obtained from each method. Using %AcINH with the conventional antimode of 70%, the number of slow acetylator was 12.7%. Using AcINH/INH, the number of slow acetylator was 52% according to the conventional antimode of 6.0. The molar metabolic ratio INH/AcINH showed explicitly the best bimodality and a clear-cut antimode among these three methods. From probit plots of INH/AcINH, an antimode of 0.45 can be suggested for the 434 Japanese patients; 377 patients (86.9%) as rapid acetylator and 57 patients (13.1%) as slow acetylator.