Acetylator phenotype and metabolic disposition of isoniazid in Japanese patients with systemic lupus erythematosus.

Abstract

Acetylator phenotype and metabolic disposition of isoniazid (INH) were studied in 19 Japanese (a population shown to be 11.5% slow acetylators) patients with spontaneous systemic lupus erythematosus (SLE) and 19 healthy controls. Subjects with the elimination half-life (t1/2) of INH of 2.0 hours or less were considered rapid and those of 2.2 hours or more were slow acetylators. Results of phenotyping showed that 17 of 19 SLE patients were rapid, 1 slow, and 1 indeterminate, whereas 18 of the controls were rapid and 1 indeterminate. When phenotyped according to another reported antimode (107 or 110 minutes), 3 of the patients and 2 of the controls were slow and the remainder were all rapid acetylators. The distribution of INH t1/2, acetyl INH to INH ratios in urine and plasma, and hydrazine compounds in urine measured with gas chromatography mass spectrometry was similar between the two groups, except for 1 patient who was definitely classified as a slow acetylator. The relationship between phenotype distribution and possible pathoetiologic factors is discussed.