Understanding outliers on the usual dose-response curve: venlafaxine as a way to phenotype patients in terms of their CYP 2D6 status and why it matters.

Preskorn SH

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Understanding outliers on the usual dose-response curve: venlafaxine as a way to phenotype patients in terms of their CYP 2D6 status and why it matters.

机译：了解通常的剂量反应曲线上的异常值：文拉法辛是根据CYP 2D6状态及其重要性来表型化患者的一种方法。

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Venlafaxine is a model substrate for the drug metabolizing cytochrome P450 (CYP) enzyme 2D6. The desvenlafaxine/venlafaxine ratio, either after a single dose or at steady state, can be used to determine whether a patient is functionally (i.e., phenotypically) a CYP 2D6 extensive or poor metabolizer (EM or PM). In turn, CYP 2D6 EM and PM status is important in determining the efficacy of venlafaxine as an antidepressant. Based on a secondary analysis of four of the venlafaxine registration trials, venlafaxine was effective in patients who were CYP 2D6 EMs versus a parallel placebo-treated control group, whereas it was not effective in patients who were CYP 2D6 PMs. Thus, venlafaxine is a useful example of how drugs can be used to quantify differences in drug metabolizing capacity among patients and how such differences can in turn affect the efficacy of a drug (i.e., make a patient an outlier on the usual dose-response curve).

机译：Venlafaxine是药物代谢细胞色素P450（CYP）酶2D6的模型底物。单次给药后或稳定状态下的去甲文拉法辛/文拉法辛比值可用于确定患者是否在功能上（即表型上）是CYP 2D6广泛代谢或代谢不良（EM或PM）。反过来，CYP 2D6的EM和PM状态对于确定文拉法辛作为抗抑郁药的疗效也很重要。根据对四个venlafaxine注册试验的次要分析，venlafaxine在CYP 2D6 EM的患者中较在平行安慰剂治疗的对照组中有效，而在CYP 2D6 PM的患者中则无效。因此，文拉法辛是一个有用的例子，说明如何使用药物来量化患者之间药物代谢能力的差异，以及这种差异又如何影响药物的功效（即，使患者在通常的剂量反应曲线上成为异常值））。

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《Journal of psychiatric practice.》 |2010年第1期|共4页
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Preskorn SH;
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中图分类神经病学与精神病学;
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1. Understanding outliers on the usual dose-response curve: venlafaxine as a way to phenotype patients in terms of their CYP 2D6 status and why it matters. [J] . Preskorn SH Journal of psychiatric practice. . 2010,第1期

机译：了解通常的剂量反应曲线上的异常值：文拉法辛是根据CYP 2D6状态及其重要性来表型化患者的一种方法。
2. CYP2D7–2D6 hybrid tandems: identification of novel CYP2D6 duplication arrangements and implications for phenotype prediction [J] . Andrea Gaedigk, Uwe Fuhr, Charlene Johnson, Pharmacogenomics . 2010,第1期

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3. Patients who do not respond to the "usual" dose: why Terry fell off the dose-response curve. [J] . Preskorn SH Journal of psychiatric practice. . 2009,第6期

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Understanding outliers on the usual dose-response curve: venlafaxine as a way to phenotype patients in terms of their CYP 2D6 status and why it matters.

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