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Effect of Genetic Polymorphisms of SLC28A1, ABCG2, and ABCC4 on Bioavailability of Mizoribine in Healthy Japanese Males

The aim of the present study was to investigate the genetic factors responsible for the interindividual variability in the bioavailability of mizoribine. Thirty healthy Japanese men aged 20–49 years and weighing 53–75kg participated in the present study and took 150mg of mizoribine. Urine samples we...

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Bibliographic Details
Published in:DRUG METABOLISM AND PHARMACOKINETICS 2011-01, Vol.26 (5), p.538-543
Main Authors: Fukao, Miki, Ishida, Kazuya, Sakamoto, Takuya, Taguchi, Masato, Matsukura, Hiroyoshi, Miyawaki, Toshio, Hashimoto, Yukiya
Format: Article
Language:English
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Summary:The aim of the present study was to investigate the genetic factors responsible for the interindividual variability in the bioavailability of mizoribine. Thirty healthy Japanese men aged 20–49 years and weighing 53–75kg participated in the present study and took 150mg of mizoribine. Urine samples were collected periodically for 12h after the dose, and the bioavailability of mizoribine was calculated from the estimated total urinary excretion from time zero to infinity. The bioavailability of mizoribine in the 30 subjects ranged from 60.3% to 99.4%. The mean bioavailability of mizoribine in subjects with the concentrative nucleoside transporter 1 (SLC28A1) 565-A/A allele (75.4%) was significantly lower than that in subjects with the SLC28A1 565-G/G allele (90.1%). On the other hand, the bioavailability of mizoribine was not affected by polymorphisms of breast cancer resistance protein (ABCG2) C421A and multidrug resistance-associated protein 4 (ABCC4) G2269A. The findings in the present prospective study suggested that the genetic test for the SLC28A1 G565A polymorphism is promising for predicting the Japanese subjects with lower bioavailability of mizoribine.
ISSN:1347-4367
1880-0920
DOI:10.2133/dmpk.DMPK-11-NT-040