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CYP2D6 多态性与产后疼痛管理中的可待因镇痛:一项初步研究。

CYP2D6 polymorphisms and codeine analgesia in postpartum pain management: a pilot study.

机构信息

Department of Pharmaceutical Sciences, University of Toronto, Ontario, Canada.

出版信息

Ther Drug Monit. 2011 Aug;33(4):425-32. doi: 10.1097/FTD.0b013e3182272b10.

Abstract

BACKGROUND

Codeine, a common opiate prescribed for pain postcesarean section (c-section), is biotransformed by the highly polymorphic Cytochrome P450 enzyme 2D6 (CYP2D6). Ultrarapid metabolizers (UMs), individuals with multiple active copies of CYP2D6, can biotranform up to 50% more codeine into morphine than normal individuals can. In contrast, poor metabolizers (PMs), individuals who have no active CYP2D6 genes, convert almost no codeine into morphine and as a result may take multiple doses of codeine without attaining analgesia.

OBJECTIVE

The aim was to study the relationship between CYP2D6 genotype and codeine analgesia among women recovering from c-section.

METHODS

Forty-five mothers prescribed codeine provided a blood sample for CYP2D6 genotyping and recorded their pain level 4 times a day for 3 days immediately after a c-section. Codeine was used on an as-needed basis; doses and times were recorded. The relationship between CYP2D6 genotype, pain scores, need for codeine, and adverse events was studied. Theoretical morphine dose, based on CYP2D6 genotype, was estimated.

RESULTS

Women at the genotypic extremes reported codeine effects consistent with their genotype: the 2 PMs of codeine reported no analgesia as a result of taking codeine, whereas 2 of the 3 UMs reported immediate pain relief from codeine but stopped taking it due to dizziness and constipation. Much larger numbers are needed to study similar correlations among extensive and intermediate metabolizers.

CONCLUSIONS

In this pilot study, the extreme CYP2D6 genotypes (PMs and UMs) seemed to predict pain response and adverse events. Larger sample sizes are needed to correlate the range of genotypes with pain response.

摘要

背景

可待因是一种常用于剖宫产(c-section)后止痛的常见鸦片类药物,它通过高度多态的细胞色素 P450 酶 2D6(CYP2D6)进行生物转化。超快代谢者(UM)是指有多个活性 CYP2D6 拷贝的个体,他们可以将高达 50%的可待因转化为吗啡,而正常个体则无法做到。相比之下,弱代谢者(PM)是指没有活性 CYP2D6 基因的个体,他们几乎无法将可待因转化为吗啡,因此可能需要多次服用可待因才能达到止痛效果。

目的

本研究旨在探讨 CYP2D6 基因型与剖宫产术后女性可待因镇痛之间的关系。

方法

45 名接受可待因治疗的母亲提供了一份血液样本进行 CYP2D6 基因分型,并在剖宫产术后立即的 3 天内每天 4 次记录她们的疼痛程度。可待因按需使用,记录剂量和使用时间。研究了 CYP2D6 基因型、疼痛评分、对可待因的需求以及不良反应之间的关系。根据 CYP2D6 基因型估计了理论上的吗啡剂量。

结果

可待因基因型处于极端的女性报告的可待因效果与其基因型一致:2 名可待因 PM 患者由于服用可待因而没有止痛效果,而 3 名可待因 UM 中的 2 名患者立即从可待因中缓解疼痛,但因头晕和便秘而停止服用。还需要更多的研究来研究广泛和中度代谢者之间的类似相关性。

结论

在本试点研究中,极端 CYP2D6 基因型(PM 和 UM)似乎可以预测疼痛反应和不良反应。需要更大的样本量来将基因型范围与疼痛反应相关联。

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