Effect of age and smoking on in vivo CYP1A2, flavin-containing monooxygenase, and xanthine oxidase activities in Koreans: determination by caffeine metabolism.

Abstract

To assess the effect of gender, age, and smoking habits on the in vivo activities of CYP1A2, flavin-containing monooxygenase (FMO), and xanthine oxidase in Korean subjects. One hundred thirty-three age- and gender-matched healthy Korean volunteers (age range, 21 to 78 years; mean age, 35.3 +/- 16.6 years) with and without smoking habits participated. After drinking a cup of coffee (200 mL) that contained 110 mg caffeine, a 1-hour urine sample (between 4 and 5 hours) was collected and caffeine metabolites were analyzed by HPLC. There were marked individual variations in CYP1A2 [(1,7-dimethylurate + paraxanthine)/caffeine], FMO (theobromine/caffeine), and xanthine oxidase (1-methylurate/1-methylxanthine) activities (14-, 42-, and 9-fold, respectively). However, the mean values of these enzyme activities in the nonsmokers were not different between men and women. In the nonsmoking subjects in their 20s, the mean values 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 older decennial age groups. Xanthine oxidase activities were the same for all age groups (subjects in their 20s through their 70s). CYP1A2 activity of the smokers (20.0 +/- 9.6) was higher than that of the nonsmokers (10.8 +/- 5.8; P < .001). Similarly, the FMO activity in smokers (3.4 +/- 2.7) was higher than that of the nonsmokers (1.8 +/- 1.7; P < .001). The xanthine oxidase activity (1.3 +/- 0.5) was not increased in smokers (1.4 +/- 0.5; P = .46). Results of this caffeine metabolism study conducted with age- and gender-matched healthy Korean volunteers with and without smoking habits provided the baseline and the widely varying interindividual activities of CYP1A2, FMO, and xanthine oxidase in a Korean population. The results also suggested that drugs metabolized by CYP1A2 and FMO may require individualized dose adjustment according to the age and smoking habits of the subjects.