Isoniazid disposition, comparison of isoniazid phenotyping methods in and acetylator distribution of Japanese patients with idiopathic systemic lupus erythematosus and control subjects.

1 Plasma levels of isoniazid (INH) and acetyl INH in plasma were measured with a spectrofluorometric method, and INH and its metabolites (acetyl INH, mono-acetylhydrazine, diacetylhydrazine and free hydrazine) excreted in urine were measured with a gas chromatography-mass spectrometry, respectively, after an oral dose of INH 10 mg/kg in 19 Japanese patients with idiopathic systemic lupus erythematosus (SLE) and in the same number of healthy controls. 2 When phenotyped according to various methods previously reported, 16 to 18 of the SLE and 17 to 19 of the control group were rapid acetylators. Regardless of the phenotyping methods applied, the distribution of acetylator phenotype of SLE patients was not significantly different from the control group or from the data previously reported among normal Japanese population. 3 By phenotyping our subjects with an INH T 1/2 of 110 min or less as rapid acetylators, and more slow acetylators, 3 of SLE patients and 2 of the controls were slow, while the remainder were all rapid. When this antimode was used, the mean apparent kinetic variables of INH and acetyl INH estimated from the plasma concentration-time data and the mean values for the 24-h urinary amount of INH and its metabolites, except for monoacetylhydrazine (P less than 0.05), did not significantly differ between the rapid acetylators of SLE and control groups. 4 The distribution of INH T 1/2, acetyl INH to INH ratios in plasma and urine, values in urine for log10 (diacetylhydrazine to monoacetylhydrazine) and for diacetylhydrazine to INH or acetyl INH was similar between the two groups except for one patient who was definitely classified as a slow acetylator regardless of whichever phenotyping methods were used. The excretory patterns of hydrazine compounds reflect, in general, the inactivating ability of INH in each individual. 5 The data suggest that phenotyping by using plasma samples is, in general, better than by using urine samples. The plasma T 1/2 alone is the most satisfactory criterion. 6 We conclude that neither INH disposition nor phenotype distribution assessed by the reported methods using INH as the test compound are altered in idiopathic SLE, and that a search for racial and/or geographical factor(s) likely to result in autoimmune disease may give a clue to the pathogenesis in addition to further exploration for the possible interrelation between idiopathic SLE and genetic slow acetylation.