Evaluation of caffeine as an in vivo probe for CYP1A2 using measurements in plasma, saliva, and urine
Evaluation of caffeine as an in vivo probe for CYP1A2 using measurements in plasma, saliva, and urine
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DOI：
10.1097/00007691-200008000-00008
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发表时间：
2000-08-01
影响因子：
2.5
通讯作者：
Bertilsson, L
中科院分区：
文献类型：
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作者：
Carrillo, JA;Christensen, M;Bertilsson, L
25名健康志愿者口服100 mg咖啡因，并对细胞色素P450 1A 2（CYP 1A 2）活性进行了评估。验证是通过将血浆、唾液和尿液中的不同参数与作为参考标准的两种咖啡因清除率测量值CL（口服）和CL（137 X-> 17 X）相关联而形成的。两名受试者因不遵守无咖啡因饮食而被排除。在其余23名受试者中，血浆和唾液中咖啡因的总清除率彼此高度相关（r（s）= 0.97，p < 0.0001）。仅限于给药后4小时采集的一个采样点的比值17 X/137 X显示与CL（经口）和CL的高度相关性（r（s））（137 X--> 17 X）血浆（0.84/0.83）和唾液（0.82/0.77）（所有相关值p < 0.0001），其中1,7 X是1，7-二甲基黄嘌呤（副黄嘌呤），1,3,7 X是1，3，7-三甲基黄嘌呤（咖啡因）。此外，Ratio 0-24 h尿中（AFMU + 1U + 1X +17 U +17 X）/137 X与CL的相关性最高（137 X-> 17 X）（r（s）= 0.85，p < 0.001），其中AFMU是5-乙酰氨基-6-甲酰氨基-3-甲基尿嘧啶，1U是1-甲基尿嘧啶，1X是1-甲基黄嘌呤，17 U是1，7-二甲基尿酸。CYP 1A 2活性的主要估计值在不吸烟女性中显著较低，这可能与该亚群中口服避孕药的使用有关。总之，在基于咖啡因的CYP 1A 2方法中，作者建议在至少8小时的采样间隔期间，从摄入咖啡因后的零时间开始，测量血浆或唾液17 X/137 X比值和尿液（AFMU + 1U + 1X +17 U +17 X）/137 X比值。这些指数是用于人群研究的CYP 1A 2活性的简单、可靠和相对便宜的估计。
Twenty-five healthy volunteers were given 100 mg caffeine orally and several estimates of cytochrome P450 1A2 (CYP1A2) activity were evaluated. The validation was pet-formed by correlation of different parameters in plasma, saliva, and urine to two measures of caffeine clearance, CL(oral) and CL(137X-->17X) that served as standards of reference. Two subjects were excluded because of noncompliance with a caffeine-free diet. In the remaining 23 subjects, both plasma and saliva total clearances of caffeine were highly correlated with each other (r(s) = 0.97, p < 0.0001). The ratio 17X/137X restricted to one sampling point taken 4 hours after dose, showed a high correlation (r(s)) with CL(oral) and CL(137X-->17X) in plasma (0.84/0.83) and saliva (0.82/0.77) (p < 0.0001 for all the correlation values) where 17X is 1,7-dimethylxanthine (paraxanthine) and 137X is 1,3,7-trimethylxanthine (caffeine). Additionally, the ratio (AFMU + 1U + 1X + 17U + 17X)/137X in a 0-24 hours urine sampling showed the highest correlation with CL(137X-->17X) (r(s) = 0.85, p < 0.001) where AFMU is 5-acetylamino-6-formylamino-3-methyluracil, 1U is 1-methyluracil, 1X is I-methylxanthine, and 17U is 1,7-dimethyluric acid. The major estimates of CYP1A2 activity were significantly less in nonsmoking females, and this probably was related to the use of oral contraceptives in this subpopulation. In summary, among caffeine-based approaches for CYP1A2, the authors recommend either plasma or saliva 17X/137X ratio and the urinary (AFMU + 1U + 1X + 17U + 17X)/137X ratio during a sampling interval of at least 8 hours, starting at time zero since caffeine intake. These indices are simple, reliable, and relatively inexpensive estimates of CYP1A2 activity to be used in the study of human populations.