新的抗抑郁药物的代谢。概述的药理学和药代动力学的影响。

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新的抗抑郁药物的代谢。概述的药理学和药代动力学的影响。

Pharmacokinet。1998年4月,34 (4):281 - 302。doi: 10.2165 / 00003088-199834040-00002。

PubMed ID

9571301 (在PubMed

]

文摘

几种化学无关的代理一直在过去的十年中,开发和引进补充前面的抗抑郁药。这些包括5 -羟色胺的再摄取抑制剂的选择性5 -羟色胺再摄取抑制剂(SSRI)或去甲肾上腺素(西)或(milnacipran和文拉法辛),以及药物与不同的神经化学资料如米氮平、奈法唑酮、moclobemide tianeptine。像早期的药物,这些新型抗抑郁药几乎完全biotransformed排泄之前,除了milnacipran的间隙似乎同样是由于尿排泄和代谢。有时——比如moclobemide——20在体液代谢物已确定。然而,在某些情况下,只有少数代谢物被检测到,相当比例的剂量仍下落不明(如氟西汀、氟伏沙明)。代谢通常通过顺序或并行氧化途径。这些可能是由生理和病理因素不同程度的影响和由细胞色素P450 (CYP) 2 d6和CYP2C19基因多态性。一些影响手性(如西酞普兰的脱烷基化作用和氟西汀),尽管仍然缺乏这方面的配置信息为其他药物现有外消旋体(如米氮平和tianeptine)和milnacipran,这可能是4立体异构体的混合物。其他再饱和治疗剂量范围内(如某些代谢途径的氟西汀、氟伏沙明、奈法唑酮、帕罗西汀、文拉法辛)。这也许可以解释个体差异与所有这些药物,从药代动力学的角度来看,与代理三环是一样的。 Our knowledge of the isoenzymes involved in the various oxidation pathways and their relevance for potential drug interactions varies from a considerable amount for most of the SSRI and nefazodone, to minimal for reboxetine and tianeptine. This information is useful for predicting the pharmacokinetic interactions mediated through inhibition of specific isoenzymes. This would be better appreciated if the enzymatic mechanisms involved in the biotransformation of the metabolite(s), and their role in drug interactions, were also known. This information is still lacking for some drugs, although metabolites may exhibit in vitro inhibitory potencies of similar to (paroxetine and its M2 metabolite as inhibitors of CYP2D6) or even greater than that of the parent drug (norfluoxetine is more potent than fluoxetine as an inhibitor of CYP3A3/4, and in view of the longer half-life (t1/2) of the metabolite the potential for interactions may persist for weeks after discontinuation of the parent drug). While we do know something about the biological activity of the metabolites of some of these drugs, we know very little about others. With few exceptions this knowledge refers only to the major metabolite(s) and regards the main in vitro effects as exerted by the parent drug. However, in vitro potency and selectivity may not translate directly into in vivo, and either major or minor metabolites may have characteristic in vitro and in vivo properties. For example, unlike the parent drug some minor ring-opened metabolites of moclobemide have monoamine oxidase-B inhibitory activity in the rat, and the nefazodone metabolite m-chlorophenyl-piperazine shows activity on 5-HT2C receptors in rats and humans. Data on the brain-to-blood partition of metabolites compared with their parent drug are available only in a few cases. They are still not known for the main metabolites of fluvoxamine, milnacipran, mirtazapine, moclobemide, nefazodone, paroxetine, reboxetine and venlafaxine, despite the fact that total blood concentrations do not always reflect the metabolite: parent drug ratio in brain. Thus, in most cases, we do not really know what part hepatic metabolism plays in the overall effect of the administered parent drug.

DrugBank数据引用了这篇文章

药物

西酞普兰

药物酶

药物	酶	类	生物	药理作用	行动
Tianeptine	细胞色素P450 3 a4	蛋白质	人类	没有	底物	细节

食物相互作用

药物	交互
Tianeptine	与葡萄柚产品的),运动则要谨慎。葡萄柚抑制CYP3A4代谢,这可能会增加tianeptine的血清浓度。
Tianeptine	圣约翰草的),运动则要谨慎。该草本诱发CYP3A新陈代谢,降低tianeptine的血清水平。