A population phenotyping study of three drug-metabolizing enzymes in Kyushu, Japan, with use of the caffeine test.
OBJECTIVE
We assessed in vivo activities of cytochrome P450 1A2 (CYP1A2), N-acetyltransferase 2, and xanthine oxidase in Japanese residents of Kyushu, the southern island of Japan.


METHODS
One hundred eighty-two healthy volunteers (108 men and 74 women) received a 150-mg oral dose of caffeine before they went to sleep. The concentrations of caffeine, caffeine metabolites, and uric acid in their overnight urine samples were analyzed. The CYP2A6 genotypes were determined in 66 of the 182 volunteers to assess whether they affected a metabolic ratio for CYP1A2 activity index.


RESULTS
The metabolic ratio for CYP1A2 was not polymorphic, but its mean ratio was greater in smokers than in nonsmokers (P <.05). Twenty subjects (11.0%) were found to be slow acetylators. Twenty subjects were determined to be putative poor metabolizers of xanthine oxidase, and the mean urinary uric acid concentration of those subjects was 53% lower than that of the other subjects (P <.0001). The mean ratio for CYP1A2 obtained from 3 subjects with the CYP2A6(*)4C/CYP2A6(*)4C genotype was greater than the mean ratio from subjects with other genotypes (P <.01) or that from subjects with a wild-type CYP2A6(*)1A allele (P <.05).


CONCLUSIONS
Our results suggest that putative poor metabolizers of xanthine oxidase activities exist in a Japanese population and that a decreased 1,7-dimethyluric acid formation from caffeine in poor metabolizers of CYP2A6 appears to affect the metabolic ratio used for the assessment of CYP1A2 activity.
Department of Pharmacology and Therapeutics, Graduate School of Clinical Pharmacy, Kumamoto University, Oe-honmachi 5-1, Kumamoto 862-0973, Japan.
Junji
J
Saruwatari
Kazuko
K
Nakagawa
Junichi
J
Shindo
Takahiro
T
Tajiri
Masaki
M
Fujieda
Hiroshi
H
Yamazaki
Tetsuya
T
Kamataki
Takashi
T
Ishizaki
D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics*; D002110:Caffeine / Q000378:metabolism*; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D010641:Phenotype; D012016:Reference Values; D014527:Uric Acid / Q000652:urine; D014969:Xanthine Oxidase / Q000235:genetics* / Q000378:metabolism
D014527:Uric Acid; D002110:Caffeine; D019388:Cytochrome P-450 CYP1A2; D014969:Xanthine Oxidase; D001191:Arylamine N-Acetyltransferase