카페인을 이용한 Flavin-containing monooxygenase 효소 활성도 검색

초록

To examine the individual variation in drug metabolism catalyzed by flavin-containing monooxygenase (FMO), urinary molar concentration ratio of theobromine (TB) and caffeine (CA) has been determined in 179 Korean volunteers. The 1 hr urine (between 4 and 5 hrs) was collected at 5 hr following administration of a cup of coffee containing 115 mg CA and analyzed using an HPLC system. The lowest TB/CA ratio was 0.40 and the highest ratio was 15.17 (38 fold difference) and the median ratio for all subjects was 1.87 and the mean was 2.66 with 2.36 S.D.. In the 134 nonsmokers (51 male and 83 female subjects), the mean ratio was 2.35 1.93 and for the 45 male smokers, it was 3.62 3.19 and the frequency distribution of this ratio for smokers was significantly higher than that of the nonsmokers (Mann-Whitney test; p = 0.003). This indicated that the FMO activity in smokers was increased. There were no smokers among the 83 female volunteers. Comparing the ratio in 51 nonsmokers and 45 smokers among the 96 male subjects, the respective mean values were 2.30 2.26 for the male and 2.37 1.85 for the female, respectively, and they were not significantly different (p=0.518). This indicated that there was no gender difference in the FMO activity. When the normal test variable (NTV) plot was applied, the minimal NTV values for total subjects (-0.04), nonsmokers (-0.05) and smokers (-0.08) suggested a bimodal distribution of FMO activity in human. The assumed antimode values obtained from NTV plots were 3.16 for the total subjects, 3.16 for the nonsmokers and 4.50 for the smokers. The number of subjects with TB/CA ratio over the assumed antimode, extensive metabolizers, were 50 (27.9%) among the total of 179, 12 (26.7%) among 45 smokers and 32 (23.9%) among 134 nonsmokers. In conclusion, the FMO activity in human shows marked individual variatio