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[抗抑郁药的药代动力学与药物相互作用]

[Pharmacokinetics and drug interactions of antidepressive agents].

作者信息

Sawada Y, Ohtani H

机构信息

Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University.

出版信息

Nihon Rinsho. 2001 Aug;59(8):1539-45.

Abstract

Tricyclic antidepressive agents(TCAs) are conventional antidepressant. Cytochrome P450(CYP) 2D6 is involved in the hydroxylation of TCAs, while N-demethylation of TCAs is mediated by other such as CYP2C19, 3A4 and 1A2. The elimination of TCAs is impaired by CYP2D6 inhibitors such as quinidine. Newer antidepressants, selective serotonin uptake inhibitors(SSRIs), are also metabolized in the liver. Fluvoxamine, an SSRI, is a potent inhibitors for CYP1A2 and CYP2C19, moderate for CYP3A4 and weak for CYP 2D6. Paroxetine, another SSRI, causes substantial inhibition of CYP2D6 activity. Milnacipran, a serotonin and noradrenaline reuptake inhibitor, is mainly excreted unchanged in urine and some part as its glucronide conjugate. In contrast to many SSRIs, milnacipran is devoid of metabolic inhibition.

摘要

三环类抗抑郁药(TCAs)是传统的抗抑郁药。细胞色素P450(CYP)2D6参与三环类抗抑郁药的羟基化作用,而三环类抗抑郁药的N-去甲基化则由其他酶介导,如CYP2C19、3A4和1A2。三环类抗抑郁药的消除会受到CYP2D6抑制剂(如奎尼丁)的影响。新型抗抑郁药,即选择性5-羟色胺再摄取抑制剂(SSRIs),也在肝脏中代谢。氟伏沙明是一种选择性5-羟色胺再摄取抑制剂,是CYP1A2和CYP2C19的强效抑制剂,对CYP3A4为中度抑制,对CYP2D6为弱抑制。另一种选择性5-羟色胺再摄取抑制剂帕罗西汀会显著抑制CYP2D6的活性。米那普明是一种5-羟色胺和去甲肾上腺素再摄取抑制剂,主要以原形经尿液排泄,部分以其葡糖醛酸共轭物的形式排泄。与许多选择性5-羟色胺再摄取抑制剂不同,米那普明没有代谢抑制作用。

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