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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.


Miyuki Kimura, Makiko Shimizu, Kazuma Kiyotani, Kazuko Nakagawa, Tetsuya Kamataki, Hiroshi Yamazaki. Cytochrome P450 2A6 phenotyping based on dietary caffeine intake in a Japanese population of non-smokers. Drug metabolism letters. 2012 Jun 1;6(2):67-72

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PMID: 22849705

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