细胞色素P450 (CYP) 2D6酶代谢的精神药物及其相互作用

G. Ayano
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引用次数: 9

摘要

本文综述了由细胞色素P450 (CYP) 2D6代谢的精神药物,并讨论了这种代谢与药物相互作用的可能相关性。CYP2D6是细胞色素P450超家族的一员,在70多种底物药物的代谢中起主要作用,包括抗抑郁药、抗精神病药、情绪稳定药、抗癫痫药、受体阻滞剂、止吐药、阿片类药物和镇静/催眠药。它负责约25%的常用处方药的代谢。CYP2D6主要代谢四种典型的抗精神病药物,如氟哌啶醇、氯丙嗪、硫硝嗪和非那嗪,以及第二代抗精神病药物中的利培酮。去甲替林、帕罗西汀、氟西汀、文拉法辛和地西帕明是抗抑郁药,主要由CYP2D6代谢。普萘洛尔、美托洛尔、替马洛尔和阿佩洛尔是常见的受体阻滞剂,主要由CYP2D6代谢。经CYP2D6代谢的药物可抑制或诱导该酶的作用。抑制CYP2D6的药物可预见地增加药物的血浆浓度或减少底物的清除。安非他酮、氟西汀、帕罗西汀、诺瑞辛酮、西酞普兰、艾司西酞普兰、舍曲林、氟伏沙明、奈法唑酮、文拉法辛、氯丙咪嗪、可卡因、奎尼丁和雷尼替丁等药物是CYP2D6酶的抑制剂。与与CYP2D6一起代谢90%药物的CYP1A2、CYP2C9、CYP2C19、CYP3A4和CYP3A5酶不同,CYP2D6没有明显的诱导剂。
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Psychotropic Medications Metabolized by Cytochromes P450 (CYP) 2D6 Enzyme and Relevant Drug Interactions
Psychotropic medications metabolized by cytochromes P450 (CYP) 2D6 are reviewed, and the possible relevance of this metabolism to drug-drug interactions is discussed. CYP2D6 is a member of the cytochrome P450 super family and it plays a primary role in the metabolism of more than 70 substrate medications, belonging to classes such as antidepressants, antipsychotics, mood stabilizers, antiarthemics, beta blockers antiemetics, opoid and Sedative/ hypnotics. It is responsible for the metabolism of about 25% of the commonly prescribed drugs. CYP2D6 Primarily metabolizes four of the typical antipsychotic medications, such as haloperidol, chlorpromazine, thioridazine and perphenazine, and risperidone from second generation antipsychotics. Nortriptyline, paroxetine, fluoxetine, venlafaxine and desipramine are antidepressants which are primarily metabolized by CYP2D6. Propranolol, metoprolol, timolol and alperolol are among the common beta blockers which are primarily metabolized by CYP2D6. Drugs which are metabolized by CYP2D6 may inhibit or induce the action of the enzyme. Drugs that inhibit CYP2D6 will predictably increase the plasma concentrations of the medications or decrease in clearance of substrates. Drugs such as bupropion, Fluoxetine, Paroxetine, norethindrone Citalopram, Escitalopram, Sertraline, Fluvoxamine, Nefazodone, Venlafaxine, clomipramine, cocaine, quinidine, and ranitidine are inhibiters of CYP2D6 enzyme. Unlike CYP1A2, CYP2C9, CYP2C19, CYP3A4 and CYP3A5 enzymes which together with CYP2D6 metabolizes 90 percent of drugs CYP2D6 has no significant inducers.
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