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 and S-mephenytoin 4-hydroxylation phenotypings using the respective test 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 rs values > 0.84; p < 0.001), the cocktail phenotyping assessment was extended to the other 74 Indonesians. In a total of 104 Indonesians phenotyped with the cocktail test, a visual antimode was apparent only in the dapsone 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 interval, 8.5% to 22.3%), respectively. The distribution histogram and probit plots of the metabolic ratio of metoprolol gave no clear evidence for bimodality, and therefore no poor alpha-hydroxylator of metoprolol was considered to exist in the present sample size. The findings indicate that the Indonesian subjects have a greater incidence of slow acetylator phenotype compared with Japanese and Chinese, as well as a frequency of poor metabolizer phenotype of S-mephenytoin similar to that of Korean and Chinese subjects. They resemble an African population (Nigerians) in metoprolol alpha-hydroxylation polymorphism, with no apparent antimode derived from white populations.
Setiabudy
R
R
Department of Pharmacology, School of Medicine, University of Indonesia, Jakarta.
Kusaka
M
M
Chiba
K
K
Darmansjah
I
I
Ishizaki
T
T
D000107:Acetylation; D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D002681:China; D003622:Dapsone / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D006900:Hydroxylation; D007214:Indonesia; D007564:Japan; D008297:Male; D008617:Mephenytoin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D008790:Metoprolol / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics
D003622:Dapsone; D008790:Metoprolol; D008617:Mephenytoin