选择性5 -羟色胺再摄取抑制剂的临床药物动力学。

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范Harten J

选择性5 -羟色胺再摄取抑制剂的临床药物动力学。

Pharmacokinet。1993年3月,24 (3):203 - 20。doi: 10.2165 / 00003088-199324030-00003。

PubMed ID

8384945 (在PubMed

]

文摘

功能共同选择性5 -羟色胺再摄取抑制剂(SSRIs)是他们认为作为抗抑郁药物,因为它们能够可逆地阻止5 -羟色胺的再摄取(5 -羟色胺;5)突触间隙。从化学的角度来看,然而,他们显示出明显的差异。因此,药物的药代动力学行为是非常不同的,而这些药代动力学差异可能产生重大影响的临床资料的行动。所有ssri类药物有很好的亲和力5再吸收载体在中枢神经系统的突触间隙,和更少的亲和力去甲肾上腺素再吸收载体(去甲肾上腺素),α-和该项,多巴胺、组胺、5 -和毒蝇碱受体。氟西汀和西酞普兰外消旋混合物,氟西汀的同分异构体有几乎相等的亲和力5再吸收载体,再摄取抑制剂性能的同时,几乎只存在在西酞普兰(+)异构体。Norfluoxetine,氟西汀的代谢物,有选择性的5 -再吸收载体与氟西汀相当。胃肠道吸收的ssri类药物通常是好的,血浆浓度峰值大约4至6 h后观察。西酞普兰的绝对生物利用度几乎是100%,而很可能其他化合物经历(实质性)初步的新陈代谢。明显单剂后口服间隙值的范围从26 L / h(西酞普兰)到167 L / h(帕罗西汀),而多剂量口服后间隙明显减少,特别是对氟西汀、帕罗西汀。 Plasma protein binding of fluoxetine, paroxetine and sertraline is > or = 95%; values for fluvoxamine (77%) and citalopram (50%) are much lower. For all compounds, however, protein binding interactions do not seem to be of great importance. Although many attempts were made, to date no convincing evidence exists of a relationship between plasma concentrations of any of the SSRIs and clinical efficacy. Elimination occurs via metabolism, probably in the liver. Renal excretion of the parent compounds is of minor importance. Metabolites of fluvoxamine and fluoxetine are predominantly excreted in urine; larger quantities of metabolites of paroxetine (36%) and sertraline (44%) are excreted in faeces. The half-lives of fluvoxamine, paroxetine, sertraline and citalopram are approximately 1 day. The half-life of fluoxetine is approximately 2 days (6 days after multiple doses), and that of the active metabolite norfluoxetine is 7 to 15 days. The metabolism of paroxetine, and possibly also of fluoxetine, is under genetic control of the sparteine/debrisoquine type. Available data indicate that metabolism of SSRIs is impaired with reduced liver function.(ABSTRACT TRUNCATED AT 400 WORDS)

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药物

帕罗西汀