Assessment of flavin-containing monooxygenase (FMO) activity by determining urinary ratio of theobromine and caffeine in a Korean population after drinking a cup of coffee .
- Author:
Woon Gye CHUNG
1
;
Ju Hee KANG
;
Hyung Keun ROH
;
Kyung Hoon LEE
;
Chang Shin PARK
;
Young Nam CHA
Author Information
1. Department of Pharmacology and Toxicology, College of Medicine, Inha University, Inchon, 402-751 South Korea.
- Publication Type:Original Article
- Keywords:
Ethanol;
Phosphate uptake;
Glucose uptake;
Brush-border membrane vesicles;
Rabbit kidney
- MeSH:
Caffeine*;
Chromatography, High Pressure Liquid;
Coffee*;
Cytochrome P-450 CYP1A2;
Drinking*;
Ethanol;
Female;
Humans;
Male;
Metabolism;
Molar;
Theobromine*;
Tobacco Products;
Volunteers
- From:The Korean Journal of Physiology and Pharmacology
1999;3(2):207-213
- CountryRepublic of Korea
- Language:English
-
Abstract:
To examine individual variation in drug metabolism catalyzed by flavin-containing monooxygenase (FMO), 179 Korean volunteers' urinary molar concentration ratio of theobromine (TB) and caffeine (CA) was determined. Their urine was collected for 1 hr (between 4 and 5 hrs) after they drank a cup of coffee containing 115 mg CA and analyzed by an HPLC system. The lowest TB/CA ratio obtained was 0.40, the highest ratio was 15.17 (38-fold difference), and the median ratio for all subjects was 1.87. The mean was 2.66 with 2.36 S.D.. In 134 nonsmokers, the mean ratio was 2.35 +/- 1.93, that of 51 males was 2.30 +/- 2.26 and 83 females was 2.37 +/- 1.85, respectively. There was no significant gender difference in the obtained TB/CA ratio (Mann-Whitney test; p=0.518). There were no smokers among the 83 female volunteers. In the remaining 96 male subjects, the ratio obtained in 51 nonsmokers was 2.30 +/- 2.06 and that of 45 smokers was 3.62 +/- 3.19. This indicated that the TB/CA ratio was increased significantly in smokers (p=0.007). However, when the TB/CA ratios (FMO activity) obtained in all 179 Korean volunteers are compared with the urinary concentration ratios of paraxanthine (PX) plus 1,7-dimethylurate (17U) to CA (CYP1A2 activity), there was a weak but significant correlation (Pearson's correlation coefficient test; r2=0.28, p<0.0001). This indicates that, although the urinary TB/CA ratio mostly represents FMO activity, minor contribution by CYP1A2 activity cannot be ignored. In conclusion, the FMO activity measured by taking the urinary TB/CA ratio from normal healthy Korean volunteers shows marked individual variations without significant gender differences and the increased TB/CA ratio observed in cigarette smokers may have been caused by the increased CYP1A2 activity.