Yao Chen1, Chang-Qiong Xiao1, Yi-Jing He1, Bi-Lian Chen1, Guo Wang1, Gan Zhou1, Wei Zhang1, Zhi-Rong Tan1, Shan Cao1, Li-Ping Wang1, Hong-Hao Zhou2. 1. Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Xiang-Ya School of Medicine, 110 Xiang-Ya road, Changsha, Hunan, 410078, People's Republic of China. 2. Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Xiang-Ya School of Medicine, 110 Xiang-Ya road, Changsha, Hunan, 410078, People's Republic of China. cbohua@163.com.
Abstract
PURPOSE: This study investigated the effect of 1 g genistein daily for 14 days on caffeine-based metrics of cytochrome P4501A2 (CYP1A2), cytochrome P4502A6 (CYP2A6), N-acetyltransferase 2 (NAT2), and xanthine oxidase (XO). METHODS: A single dose of 100 mg caffeine was administered once before and once on the last day of a 14-day treatment regime with 1 g genistein once daily to 18 healthy female volunteers. Urine and blood samples were collected up to 12 and 24 h, respectively, after each caffeine dose. Using high-performance liquid chromatography (HPLC), caffeine and 1,7-dimethylxanthine (17X) were quantified in plasma, whereas 17X, 1,7-dimethylurate (17U), 1-methylxanthine (1X), 1-methylurate (1U), and 5-acetylamino-6-formylamine-3-methyluracil (AFMU) were quantified in urine. Urinary metabolite ratios were calculated to assess enzyme activities and compared between administrations using analysis of variance (ANOVA). RESULTS: Genistein decreased the urinary caffeine metabolite ratio used to assess CYP1A2 activity by 41% [90% confidence interval (CI) 28-51%). The urinary ratio indicating XO activity decreased by 29% (90% CI 24-32%), whereas urinary ratio for CYP2A6 activity increased by 47% (90% CI 29-66%) after 2 weeks of genistein. The NAT2 urinary caffeine metabolite ratio did not change significantly. CONCLUSIONS: Two weeks of intake of 1 g genistein daily led to decreases in CYP1A2 and XO activity and an increase in CYP2A6 activity, whereas NAT2 activity did not change in healthy Chinese female volunteers. Pharmacokinetics of other substrates of the enzymes investigated here may be influenced in a similar manner.
PURPOSE: This study investigated the effect of 1 g genistein daily for 14 days on caffeine-based metrics of cytochrome P4501A2 (CYP1A2), cytochrome P4502A6 (CYP2A6), N-acetyltransferase 2 (NAT2), and xanthine oxidase (XO). METHODS: A single dose of 100 mg caffeine was administered once before and once on the last day of a 14-day treatment regime with 1 g genistein once daily to 18 healthy female volunteers. Urine and blood samples were collected up to 12 and 24 h, respectively, after each caffeine dose. Using high-performance liquid chromatography (HPLC), caffeine and 1,7-dimethylxanthine (17X) were quantified in plasma, whereas 17X, 1,7-dimethylurate (17U), 1-methylxanthine (1X), 1-methylurate (1U), and 5-acetylamino-6-formylamine-3-methyluracil (AFMU) were quantified in urine. Urinary metabolite ratios were calculated to assess enzyme activities and compared between administrations using analysis of variance (ANOVA). RESULTS:Genistein decreased the urinary caffeine metabolite ratio used to assess CYP1A2 activity by 41% [90% confidence interval (CI) 28-51%). The urinary ratio indicating XO activity decreased by 29% (90% CI 24-32%), whereas urinary ratio for CYP2A6 activity increased by 47% (90% CI 29-66%) after 2 weeks of genistein. The NAT2 urinary caffeine metabolite ratio did not change significantly. CONCLUSIONS: Two weeks of intake of 1 g genistein daily led to decreases in CYP1A2 and XO activity and an increase in CYP2A6 activity, whereas NAT2 activity did not change in healthy Chinese female volunteers. Pharmacokinetics of other substrates of the enzymes investigated here may be influenced in a similar manner.
Authors: Shelley S Tworoger; Dorota M Gertig; Margaret A Gates; Jonathan L Hecht; Susan E Hankinson Journal: Cancer Date: 2008-03-01 Impact factor: 6.860