个人间CYP2D6的可变性和程度的决定因素和抑制CYP1A2帕罗西汀、氟伏沙明体内。

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赫曼舒尔曼RW,奥兹德米尔V, Naranjo CA N,卖家EM,里德K, Kalow W

个人间CYP2D6的可变性和程度的决定因素和抑制CYP1A2帕罗西汀、氟伏沙明体内。

中国Psychopharmacol。1998年6月,18 (3):198 - 207。

PubMed ID

9617978 (在PubMed

]

文摘

重性抑郁症可能需要抗抑郁药物治疗了好几年。这需要考虑抗抑郁药物的长期效果在多个临床端点。抗抑郁药帕罗西汀、氟伏沙明CYP2D6的有力体外抑制剂和CYP1A2同功酶,分别。CYP2D6的间隙和CYP1A2是重要的30或更频繁地使用药物。此外,CYP1A2也促成了17个beta雌二醇代谢与代谢活化环境前致癌物(例如,香烟烟雾中芳基胺)。本研究的目的是评估个人间CYP2D6的可变性和程度的决定因素和抑制CYP1A2帕罗西汀、氟伏沙明治疗。健康志愿者和患者接受咖啡因(100毫克)和右美沙芬(30毫克)的基线和稳态帕罗西汀(10 - 20毫克/天,5 - 74天,N = 13)或氟伏沙明(50 - 100毫克/天,5-43天,N = 8)。咖啡因代谢率(CMR)和日志O-demethylation率(ODMR)的右美沙芬尿液在一夜之间被用作体内指标CYP2D6 CYP1A2和同工酶活动,分别。所有受试者CYP2D6的广泛的代谢表型。氟伏沙明治疗后,基线CMR 5.1 + / - 1.4(意思是+ / - SD)下降到2.7 + / - 1.1 (p < 0.01)。帕罗西汀对CMR没有显著影响(p > 0.05)。 In seven of eight subjects in the fluvoxamine group, posttreatment CMR was comparable with the minimum CMR value (2.0) attainable in nonsmoking healthy volunteers. After paroxetine treatment, log ODMR changed from a baseline value of -2.28 +/- 0.37 to -1.13 +/- 0.44, indicating significant inhibition of CYP2D6 (p < 0.001). Subjects' CYP2D6 phenotype did not change after paroxetine treatment. Fluvoxamine had no significant effect on log ODMR (p > 0.05). The extent of inhibition of CYP2D6 and CYP1A2 by paroxetine and fluvoxamine, respectively, displayed a positive correlation with baseline enzyme activity (p < 0.05). In addition, a negative association was found between the plasma paroxetine concentration and the CYP2D6 activity after paroxetine treatment (r = -0.47, p < 0.05). These data indicate that paroxetine and fluvoxamine treatment with minimum clinically effective doses significantly inhibit CYP2D6 and CYP1A2, respectively. The extent of inhibition of CYP2D6 by paroxetine and of CYP1A2 by fluvoxamine is dependent in part on the baseline enzyme activity. The interindividual variability in CYP2D6 inhibition by paroxetine can also be explained by variability in plasma paroxetine concentration. Most patients treated with fluvoxamine (50-100 mg/day) will reach population minimums for CYP1A2 activity. These results have potential implications for interindividual variability in the risk for drug-drug interactions mediated by CYP2D6 and CYP1A2 as well as for the disposition of 17beta-estradiol and environmental procarcinogens.

DrugBank数据引用了这篇文章

药物酶

药物	酶	类	生物	药理作用	行动
咖啡因	细胞色素P450 2 d6	蛋白质	人类	未知的	底物	细节
氟伏沙明	细胞色素P450 2 d6	蛋白质	人类	未知的	底物 抑制剂	细节