Reduction of CYP1A2 and flavin-containing monooxygenase activities in aged Koreans

초록

The effect of gender,age nd smoking nabits on the in vivo activities of CYP1A2,flavin-containing monooxygenase(FMO)and xanthine oxidase(XO)has been assessed in Koreans. Age(range:21-78years,mean:35.3±16.6)and sex-matched healthy Korean voluteers(n=133)participated.After drinking a cup of coffee containing 110mg caffeine,urinary caffeine metabolites were analysed by HPLC.There were marked individual variations in CYP1A2[(1,7-dimethylurate+ paraxanthine)/caffeine],FMO (theobromine/caffeine)and XO(1-methylurate/1-methylxanthine)activities(14-,42-and 9-fold,respectively).However the means of these enzyme activities were not different between males and females.In the non-smoking subjects in their 20s,the means of CYP1A2 and FMO activities(13.5±5.9 and 2.1±1.9,respectively)were higher than those (7.9±1.8 and 0.95±0.22)of folder decennial age groups. XO activities were the same for all age groups(20-70s). CYP1A2 activity of the smokers (20.2±9.6)was higher than that of the non-smokers(10.8±5.8)(p<0.001).Similarly,the FMO activity in smokers(3.4±2.7)was higher than that of non-smokers(1.8±1.7)(p<0.001). The XO activity (1.3±0.5)was not increased in smokers (1.4±0.5)(p=0.46).This study provided the base-line as well as widely varying inter-individual activities of CYP1A2, FMO and XO in a Korean population. Results further suggested that drugs metabolized by CYP1A2 and FMO may require individualized dose adjustment according to their age and smoking habits.