瑞波西汀的临床药物动力学,选择性去甲肾上腺素再摄取抑制剂治疗抑郁症患者。

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Fleishaker JC

瑞波西汀的临床药物动力学,选择性去甲肾上腺素再摄取抑制剂治疗抑郁症患者。

Pharmacokinet。2000年12月,39(6):413 - 27所示。

PubMed ID

11192474 (在PubMed

]

文摘

瑞波西汀是一种新型选择性去甲肾上腺素抑制剂,评估治疗抑郁症患者。瑞波西汀是一种外消旋混合物,(S, S) -(+)对映体似乎更强有力的抑制剂。然而,浓度时间曲线下的面积的比值(S, S) - (+) - (R, R) -(-)对映体体内大约是0.5。没有证据表明手性反转。不同间隙的两个对映体也可能被解释的差异蛋白质绑定。西的药物代谢动力学情况是线性以下一个或多个口服剂量高达12毫克/天的剂量。口服后的血浆浓度时间剖面最好1-compartment模型描述,和平均半衰期(约12小时)是一致的建议每天两次注射药物。瑞波西汀口服后吸收。绝对生物利用度为94.5%,最大浓度一般在2至4小时内实现。食物会影响速度,但不是在多大程度上,吸收。 The distribution of reboxetine appears to be limited to a fraction of the total body water due to its extensive (>97%) binding to plasma proteins. The primary route of reboxetine elimination appears to be through hepatic metabolism. Less than 10% of the dose is cleared renally. A number of metabolites formed through hepatic oxidation have been identified, but reboxetine is the major circulating species in plasma. In vitro studies show that reboxetine is predominantly metabolised by cytochrome P450 (CYP) 3A4; CYP2D6 is not involved. Reboxetine plasma concentrations are increased in elderly individuals and in those with hepatic or renal dysfunction, probably because of reduced metabolic clearance. In these populations, reboxetine should be used with caution, and a dosage reduction is indicated. Ketoconazole decreases the clearance of reboxetine, so that the dosage of reboxetine may need to be reduced when potent inhibitors of CYP3A4 are coadministered. Quinidine does not affect the in vivo clearance of reboxetine, confirming the lack of involvement of CYP2D6. There is no pharmacokinetic interaction between reboxetine and lorazepam or fluoxetine. Reboxetine at therapeutic concentrations has no effect on the in vitro activity of CYP1A2, 2C9, 2D6, 2E1 or 3A4. The lack of effect of reboxetine on CYP2D6 and CYP3A4 was confirmed by the lack of effect on the metabolism of dextromethorphan and alprazolam in healthy volunteers. Thus, reboxetine is not likely to affect the clearance of other drugs metabolised by CYP isozymes.

DrugBank数据引用了这篇文章

药物

瑞波西汀

药物酶

药物	酶	类	生物	药理作用	行动
瑞波西汀	细胞色素P450 3 a4	蛋白质	人类	未知的	底物 抑制剂	细节