DAPSONE N-ACETYLATION, METOPROLOL ALPHA-HYDROXYLATION, AND S-MEPHENYTOIN 4-HYDROXYLATION POLYMORPHISMS IN AN INDONESIAN POPULATION - A COCKTAIL AND EXTENDED PHENOTYPING ASSESSMENT TRIAL

We examined dapsone N-acetylation and metoprolol alpha-hydroxylation a nd S-mephenytoin 4-hydroxylation phenotypings using the respective tes t probes (dapsone and racemic metoprolol and mephenytoin) administered separately and in a cocktail manner to an Indonesian subject group (n = 30). After ascertaining that the separate and cocktail phenotyping tests of the probe drugs correlated with each other (all r(s) values > 0.84; p < 0.001), the cocktail phenotyping assessment was extended to the other 74 Indonesians. In a total of 104 Indonesians phenotyped wi th the cocktail test, a visual antimode was apparent only in the dapso ne N-acetylation and S-mephenytoin 4-hydroxylation polymorphisms: the frequencies of slow acetylators and poor hydroxylators were 43.3% (95% confidence interval, 33.7% to 52.8%) and 15.4% (95% confidence interv al, 8.5% to 22.3%), respectively. The distribution histogram and probi t plots of the metabolic ratio of metoprolol gave no clear evidence fo r bimodality, and therefore no poor alpha-hydroxylator of metoprolol w as considered to exist in the present sample size. The findings indica te that the Indonesian subjects have a greater incidence of slow acety lator phenotype compared with Japanese and Chinese, as well as a frequ ency of poor metabolizer phenotype of S-mephenytoin similar to that of Korean and Chinese subjects. They resemble an African population (Nig erians) in metoprolol alpha-hydroxylation polymorphism, with no appare nt antimode derived from white populations.