Article date: April 1988
By: Y Horai, T Ishizaki, in Volume 25, Issue 4, pages 487-494
1. The N‐acetylation of dapsone (DDS) was studied in 182 unrelated healthy Japanese subjects. The frequency of slow acetylators determined using the plasma monoacetyldapsone (MADDS) to DDS ratio (MADDS/DDS, slow acetylators less than 0.30 and rapid acetylators greater than 0.35) at 3 h after an oral dose of DDS (100 mg) was 6.6% (12 of the 182 subjects) with a 95% confidence interval of 3.8 to 11.2%. 2. The frequency distribution histogram of the plasma MADDS/DDS ratio showed an apparent trimodal pattern. However, the numbers of heterozygous (n = 105) and homozygous rapid acetylators (n = 65) derived from the observed data did not agree with those predicted for the respective rapid acetylators (n = 70, and n = 100) by applying the Hardy‐Weinberg Law, when the suggested antimode of 0.85 discriminating these two rapid acetylators was employed. 3. The incidence of slow acetylators was unexpectedly lower in the males (1.4%, 1 of the 69 subjects, with a 95% confidence interval of 0.2 to 7.7%) compared with the incidence in the females (9.7%, 11 of the 113 subjects, with a 95% confidence interval of 5.5 to 16.6%). The difference reached a marginally significant level (Fisher's exact probability test, P = 0.02). 4. The mean plasma concentration of MADDS was significantly (P less than 0.001) lower in the slow compared to the rapid acetylators and there was a highly significant correlation (rs = 0.757, P less than 0.001) between plasma MADDS levels and MADDS/DDS ratios. 5. Slow acetylators showed a significantly (P less than 0.001) lower urinary MADDS/DDS ratio and excreted less (P less than 0.001) MADDS than rapid acetylators.(ABSTRACT TRUNCATED AT 250 WORDS)
DOI: 10.1111/j.1365-2125.1988.tb03333.x
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