TY - JOUR
T1 - Dapsone N‐acetylation, metoprolol α‐hydroxylation, and S‐mephenytoin 4‐hydroxylation polymorphisms in an Indonesian population
T2 - A cocktail and extended phenotyping assessment trial
AU - Setiabudy, Rianto
AU - Kusaka, Meizoh
AU - Chiba, Kan
AU - Darmansjah, Iwan
AU - Ishizaki, Takashi
PY - 1994/8
Y1 - 1994/8
N2 - We examined dapsone N‐acetylation and metoprolol α‐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 pro‐bit plots of the metabolic ratio of metoprolol gave no clear evidence for bimodality, and therefore no poor α‐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 α‐hydroxylation polymorphism, with no apparent antimode derived from white populations. Clinical Pharmacology and Therapeutics (1994) 56, 142–153; doi:
AB - We examined dapsone N‐acetylation and metoprolol α‐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 pro‐bit plots of the metabolic ratio of metoprolol gave no clear evidence for bimodality, and therefore no poor α‐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 α‐hydroxylation polymorphism, with no apparent antimode derived from white populations. Clinical Pharmacology and Therapeutics (1994) 56, 142–153; doi:
UR - http://www.scopus.com/inward/record.url?scp=0028030327&partnerID=8YFLogxK
U2 - 10.1038/clpt.1994.117
DO - 10.1038/clpt.1994.117
M3 - Article
C2 - 8062490
AN - SCOPUS:0028030327
VL - 56
SP - 142
EP - 153
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
SN - 0009-9236
IS - 2
ER -