测定咖啡因的尿液代谢产物，以评估人体中的细胞色素P4501A2，黄嘌呤氧化酶和N-乙酰转移酶活性。,Therapeutic Drug Monitoring

当前位置： X-MOL 学术 › Ther. Drug Monit. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

测定咖啡因的尿液代谢产物，以评估人体中的细胞色素P4501A2，黄嘌呤氧化酶和N-乙酰转移酶活性。
Therapeutic Drug Monitoring ( IF 2.8 ) Pub Date : 1996-06-01 , DOI: 10.1097/00007691-199606000-00006
B B Rasmussen ₁ , K Brøsen

Affiliation

通过细胞色素P4501A2（CYP1A2），黄嘌呤氧化酶和N-乙酰基转移酶依次催化通过3-脱甲基途径的咖啡因代谢。这三种酶的活性可以通过四种咖啡因代谢物，5-乙酰氨基-6-甲酰氨基-3-甲基尿嘧啶（AFMU），1-甲基尿酸（1MU），1-甲基黄嘌呤（1MX）和1的尿代谢比来估算摄入咖啡因后，7,7-二甲基尿酸（17DMU）。已经开发出定量人类尿液中四种代谢物的方法。该方法基于一步一步，先用乙酸乙酯/ 2-丙醇萃取，然后用高效液相色谱仪进行紫外检测。AFMU，1MU和1MX的检测限为1 microM，17DMU的检测限为2 microM。日内和日间变异系数分别<3％和<7％，准确度在+/- 3％以内。该方法用于277名健康志愿者的人群研究，其中每人摄入200 mg咖啡因并在大约6小时后提供尿液样本。尿液中代谢物的浓度范围分别为AFMU，1MU，1MX和17DMU为2.1-327 microM，4.0-744 microM，4.9-598 microM和6.4-260 microM。女性中的CYP1A2比率（AFMU + 1MU + 1MX / 17DMU）显着低于男性，其中不包括吸烟者和口服避孕药者。吸烟者的CYP1A2比例高于不吸烟者，证实了吸烟对CYP1A2的诱导作用。如预期的那样，在使用口服避孕药的女性中，CYP1A2的比例显着低于未使用口服避孕药的女性。对于N-乙酰基转移酶比率（AFMU / 1MX）和黄嘌呤氧化酶比率（1MU / 1MX），在性别，吸烟习惯或口服避孕药方面均未见差异。所有结果均与先前关于人体内CYP1A2，N-乙酰基转移酶和黄嘌呤氧化酶活性的报道一致。因此，该方法在评估人体内的CYP1A2，N-乙酰基转移酶和黄嘌呤氧化酶方面在分析和生物学上均可靠。

"点击查看英文标题和摘要"

Determination of urinary metabolites of caffeine for the assessment of cytochrome P4501A2, xanthine oxidase, and N-acetyltransferase activity in humans.

Caffeine metabolism via the 3-demethylation pathway is sequentially catalyzed by cytochrome P4501A2 (CYP1A2), xanthine oxidase, and N-acetyltransferase. The activities of the three enzymes can be estimated from urinary metabolic ratios of four caffeine metabolites, 5-acetylamino-6-formylamino-3-methyluracil (AFMU), 1-methyluric acid (1MU), 1-methylxanthine (1MX), and 1,7-dimethyluric acid (17DMU), after the ingestion of caffeine. A method for quantitation of the four metabolites in human urine has been developed. The method is based on a one-step extraction with ethyl acetate/2-propanol followed by high-performance liquid chromatography with UV detection. The detection limit was 1 microM for AFMU, 1MU, and 1MX and 2 microM for 17DMU. The intraday and interday coefficients of variation were < 3% and < 7%, respectively, and the accuracy was within +/- 3%. The method was employed in a population study of 277 healthy volunteers, each of whom ingested 200 mg caffeine and provided a urine sample approximately 6 h later. The metabolite concentration ranges in the urines were 2.1-327 microM, 4.0-744 microM, 4.9-598 microM, and 6.4-260 microM for AFMU, 1MU, 1MX, and 17DMU, respectively. The CYP1A2 ratio (AFMU + 1MU + 1MX/17DMU) was significantly lower in women than in men, excluding smokers and oral contraceptive users. The CYP1A2 ratio was higher in smokers than in nonsmokers, confirming the induction of CYP1A2 by smoking. In women using oral contraceptives, the CYP1A2 ratio was, as expected, significantly lower than in women not using oral contraceptives. For the N-acetyltransferase ratio (AFMU/1MX) and the xanthine oxidase ratio (1MU/1MX), no differences were seen in terms of sex, smoking habits, or the use of oral contraceptives. All results are in agreement with previous reports on CYP1A2, N-acetyltransferase, and xanthine oxidase activities in humans. Thus, the method is both analytically and biologically reliable for the assessment of CYP1A2, N-acetyltransferase, and xanthine oxidase in humans.

更新日期：2019-11-01

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南