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Drug Metabolism Letters

Editor-in-Chief

ISSN (Print): 1872-3128
ISSN (Online): 1874-0758

Cytochrome P450 2A6 Phenotyping Based on Dietary Caffeine Intake in a Japanese Population of Non-smokers

Author(s): Miyuki Kimura, Makiko Shimizu, Kazuma Kiyotani, Kazuko Nakagawa, Tetsuya Kamataki and Hiroshi Yamazaki

Volume 6 , Issue 2 , 2012

Page: [67 - 72] Pages: 6

DOI: 10.2174/1872312811206020067

Price: $65

Sekisui-XenoTech-DML
Abstract

Phenotyping of cytochrome P450 2A6 (CYP2A6) was determined by assessing urinary caffeine metabolites in a Japanese population with a high frequency of CYP2A6 whole-gene deletion (CYP2A6*4). The levels of 1,7-dimethyluric acid (17U), 1-methylxanthine (1X), and 1,7-dimethylxanthine (17X) were measured in non-smokers whose CYP2A6 and NAT2 genotypes had been determined. Low 17U/1X ratios were observed in accumulated overnight urine samples of subjects genotyped as CYP2A6*4/*4 after caffeine treatment. The individual 17U/1X ratios in spot urine samples were almost constant before and 2–8 h after caffeine treatment, with or without prior abstention from dietary caffeine. The average 17U/1X ratios obtained from subjects with CYP2A6*4/*4 or CYP2A6*1/*4 genotypes were significantly lower than those from subjects with wild-type CYP2A6*1/*1 under dietary caffeine consumption. The present results suggest that impaired CYP2A6 function associated with CYP2A6*4/*4 could be determined using the 17U/1X ratios in spot urine samples under normal dietary caffeine consumption in Japanese non-smokers, without the need for additional caffeine administration or prior abstention from caffeine.

Keywords: Caffeine intake, CYP2A6, Japanese, phenotyping, urine samples, whole gene deletion


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