Dapsone N‐acetylation, metoprolol α‐hydroxylation, and S‐mephenytoin 4‐hydroxylation polymorphisms in an Indonesian population: A cocktail and extended phenotyping assessment trial

Rianto Setiabudy, Meizoh Kusaka, Kan Chiba, Iwan Darmansjah, Takashi Ishizaki

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34 Citations (Scopus)

Abstract

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:

Original languageEnglish
Pages (from-to)142-153
Number of pages12
JournalClinical Pharmacology & Therapeutics
Volume56
Issue number2
DOIs
Publication statusPublished - 1 Jan 1994

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