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细胞色素P450 2D6(CYP2D6)基因分型是否会影响癌症患者的羟考酮剂量、药代动力学、疼痛及不良反应?

Do CYP2D6 genotypes affect oxycodone dose, pharmacokinetics, pain, and adverse effects in cancer?

作者信息

Wong Aaron K, Vogrin Sara, Klepstad Pal, Rubio Justin, Le Brian, Philip Jennifer, Somogyi Andrew A

机构信息

Department of Palliative Care, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Department of Palliative Care, The Royal Melbourne Hospital, Parkville, Victoria, Australia.

出版信息

Pharmacogenomics. 2024;25(14-15):579-586. doi: 10.1080/14622416.2024.2430161. Epub 2024 Dec 4.

Abstract

AIMS

To examine the associations between and polymorphisms, plasma oxycodone and metabolite concentrations, and oxycodone response (dose, pain scores, and adverse effects) in people with pain from advanced cancer.

PATIENTS & METHODS: This multi-center prospective cohort study included clinical data, questionnaires (pain and adverse effects), and blood (pharmacokinetics, DNA). Negative binomial regression and logistic regression were used.

RESULTS

Within 33 participants, there were no differences in oxycodone response between CYP2D6 intermediate/poor metabolisers compared to normal metabolisers.Higher plasma noroxycodone and noroxycodone/oxycodone concentration ratios had higher odds of uncontrolled average pain (OR 2.44 (95%CI 1.00-5.95),  = 0.05 and OR 10.48 (95%CI 1.42-77.15),  = 0.02, respectively).

CONCLUSIONS

There was no observed benefit in genotyping in oxycodone response, however monitoring noroxycodone and oxymorphone concentrations warrant further examination.

摘要

目的

研究晚期癌症疼痛患者中细胞色素P450 2D6(CYP2D6)基因多态性与羟考酮及代谢物浓度之间的关联,以及羟考酮反应(剂量、疼痛评分和不良反应)。

患者与方法

这项多中心前瞻性队列研究纳入了临床数据、问卷(疼痛和不良反应)以及血液样本(药代动力学、DNA)。采用负二项回归和逻辑回归分析。

结果

在33名参与者中,与正常代谢者相比,CYP2D6中间/慢代谢者的羟考酮反应无差异。血浆中去甲羟考酮浓度及去甲羟考酮/羟考酮浓度比值较高者,平均疼痛未得到控制的几率更高(比值比分别为2.44(95%置信区间1.00 - 5.95),P = 0.05和10.48(95%置信区间1.42 - 77.15),P = 0.02)。

结论

未观察到CYP2D6基因分型对羟考酮反应有任何益处,然而,监测去甲羟考酮和羟吗啡酮浓度值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c9/11703413/a50906f75b2a/IPGS_A_2430161_F0001_OC.jpg

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