Pharmacokinetic-pharmacodynamic选择性5 -羟色胺再摄取抑制剂的关系。

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鲍曼P

Pharmacokinetic-pharmacodynamic选择性5 -羟色胺再摄取抑制剂的关系。

Pharmacokinet。1996; 12月31日(6):444 - 69。

PubMed ID

8968657 (在PubMed

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文摘

最近推出了抗抑郁药,选择性5 -羟色胺再摄取抑制剂(SSRIs)[西酞普兰、氟西汀、氟伏沙明、帕罗西汀和舍曲林),已知的临床疗效、耐受性好,相对安全。他们在化学结构不同于彼此,代谢和药代动力学性质。治疗药物监测这些化合物的广泛使用,为临床反应的血浆浓度范围内以最小的副作用似乎最优并不明确。最近几乎所有化验了ssri类药物及其代谢产物的定量测定血要么基于ssri类药物的分离通过高效液相色谱(HPLC)或气相色谱(GC)。介绍了西酞普兰、氟西汀外消旋化合物。有一些不同的药理、代谢和药物动力学父化合物及其对映体之间的脱甲基代谢物。立体选择色谱分析方法在血现在可用。关于SSRIs目前,不清楚在抑郁症患者血浆concentration-clinical有效性的关系已被证明,也没有任何有毒浓度阈值定义。这可能是由于他们的低毒性和使用剂量没有严重副作用出现。SSRIs千差万别的定性和定量相互作用与细胞色素P450 (CYP)同功酶在肝脏。 CYP2D6 is inhibited by SSRIs, in order of decreasing potency paroxetine, norfluoxetine, fluoxetine, sertraline, citalopram and fluvoxamine. This may have clinical consequences with some but not all SSRIs, when they are taken with tricyclic antidepressants. Except for citalopram and paroxetine, little is known about the enzymes which control the biotransformation of the SSRIs. There have been many reports on marked pharmacokinetic interactions between fluoxetine and tricyclic antidepressants. Fluoxetine has a stronger effect on their hydroxylation than on their demethylation. Interactions observed between fluoxetine and alprazolam, midazolam and carbamazepine seem to occur on the level of CYP3A. Fluvoxamine strongly inhibits the N-demethylation of some tricyclic antidepressants of the tertiary amine type and of clozapine. This may lead to adverse effects but augmentation with fluvoxamine can also improve response in very rapid metabolisers, as it increases the bioavailability of the comedication. Fluvoxamine inhibits with decreasing potency, CYP1A2, CYP2C19, CYP2D6 and CYP1A1, but it is also an inhibitor of CYP3A. Fluoxetine and fluvoxamine have shown to increase methadone plasma concentrations in dependent patients. Some authors warn about a combination of monoamine oxidase (MAO) inhibitors with SSRIs, as this could lead to a serotonergic syndrome. Studies with healthy volunteers suggest, however, that a combination of moclobemide and SSRIs, such as fluvoxamine, should not present serious risks in promoting a serotonin syndrome. A combination of moclobemide and fluvoxamine has successfully been used in refractory depression, but more studies are needed, including plasma-concentration monitoring, before this combined treatment can be recommended. Paroxetine is a substrate of CYP2D6, but other enzyme(s) could also be involved. Its pharmacokinetics are linear in poor metabolisers of sparteine, and non-linear in extensive metabolisers. Due to its potent CYP2D6 inhibiting properties, comedication with this SSRI can lead to an increase of tricyclic antidepressants in plasma, as shown with amitriptyline and trimipramine. CYP3A has been claimed to be involved in the biotransformation of sertraline to norsertraline. Clinical investigations (with desipramine) confirmed in vitro findings that CYP2D6 inhibition by sertraline is only moderate. (ABSTRACT TRUNCATED)

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药物酶

药物	酶	类	生物	药理作用	行动
阿米替林	细胞色素P450 2 d6	蛋白质	人类	未知的	底物	细节
西酞普兰	细胞色素P450 2 d6	蛋白质	人类	未知的	底物 抑制剂	细节
去郁敏	细胞色素P450 2 d6	蛋白质	人类	未知的	底物 抑制剂	细节
酞	细胞色素P450 2 d6	蛋白质	人类	未知的	底物 抑制剂	细节
氟伏沙明	细胞色素P450 1 a2	蛋白质	人类	未知的	底物 抑制剂	细节
氟伏沙明	细胞色素P450 2 c19	蛋白质	人类	没有	抑制剂	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
氟伏沙明	细胞色素P450 3 a4	蛋白质	人类	未知的	底物 抑制剂	细节
帕罗西汀	细胞色素P450 2 d6	蛋白质	人类	未知的	底物 抑制剂	细节
舍曲林	细胞色素P450 2 d6	蛋白质	人类	未知的	底物 抑制剂	细节
三甲丙咪嗪	细胞色素P450 2 d6	蛋白质	人类	未知的	底物	细节