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

IF 1.9 4区医学 Q3 PHARMACOLOGY & PHARMACY Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-12-04 DOI:10.1080/14622416.2024.2430161

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

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Abstract

Aims: To examine the associations between CYP2D6 and CYP3A4 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), p = 0.05 and OR 10.48 (95%CI 1.42-77.15), p = 0.02, respectively).

Conclusions: There was no observed benefit in CYP2D6 genotyping in oxycodone response, however monitoring noroxycodone and oxymorphone concentrations warrant further examination.

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CYP2D6基因型是否影响羟考酮剂量、药代动力学、疼痛和癌症的不良反应？

目的：研究晚期癌症疼痛患者CYP2D6和CYP3A4多态性、血浆羟考酮和代谢物浓度以及羟考酮反应（剂量、疼痛评分和不良反应）之间的关系。患者和方法：本多中心前瞻性队列研究包括临床资料、问卷调查（疼痛和不良反应）和血液（药代动力学、DNA）。采用负二项回归和logistic回归。结果：在33名参与者中，与正常代谢者相比，CYP2D6中度/不良代谢者对羟考酮的反应没有差异。血浆去甲氧可酮浓度和去甲氧可酮/去甲氧可酮浓度比值越高，出现不受控制的平均疼痛的几率越高(OR为2.44 （95%CI 1.00 ~ 5.95), p = 0.05； OR为10.48 (95%CI 1.42 ~ 77.15), p = 0.02）。结论：CYP2D6基因分型在羟考酮反应中没有观察到益处，但监测去甲氧可酮和羟吗啡酮浓度值得进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacogenomics 医学-药学

CiteScore

3.40

自引率

9.50%

发文量

审稿时长

4-8 weeks

期刊介绍： Pharmacogenomics (ISSN 1462-2416) is a peer-reviewed journal presenting reviews and reports by the researchers and decision-makers closely involved in this rapidly developing area. Key objectives are to provide the community with an essential resource for keeping abreast of the latest developments in all areas of this exciting field. Pharmacogenomics is the leading source of commentary and analysis, bringing you the highest quality expert analyses from corporate and academic opinion leaders in the field.