Cytochrome P450-2D6 activity in people with codeine use disorder

IF 2.9 3区医学 Q2 GENETICS & HEREDITY

Pharmacogenomics Journal Pub Date : 2023-11-09 DOI:10.1038/s41397-023-00319-6

Mark R. C. Daglish, Sarah R. Reilly, Sam Mostafa, Cameron Edwards, Thomas M. O’Gorman, Jeremy S. Hayllar

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Abstract

Compound-analgesics containing codeine (CACC) have been a common source of codeine for people seeking opioid replacement therapy (ORT) for codeine use disorder (CUD). Our previous work demonstrated no relationship between pre-treatment CACC and ORT buprenorphine doses; we hypothesised that CYP2D6 activity would partially account for this disconnection. One hundred six participants with CUD were compared to a published population sample of 5408 Australian patients. Mean age of participants with CUD at treatment entry was 35 years, with mean 6.1 years duration of CUD. Mean codeine dose was 660 mg/day (range 40–2700 mg). Mean calculated CYP2D6 activity scores were significantly higher in the codeine group (CUD 1.65 + 0.63 vs. Gen pop 1.39 + 0.65, Wilcoxon W = 347,001, p < 0.001). Pre-treatment CACC dose weakly predicted sublingual buprenorphine doses overall; there was a stronger relationship within ultrarapid metabolisers. While normal and ultrarapid metabolisers of codeine were more likely to have a diagnosis of CUD, poor or intermediate CYP2D6 metaboliser status may protect against CUD.

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可待因使用障碍患者的细胞色素P450-2D6活性。

含有可待因的复合止痛药（CACC）一直是寻求可待因使用障碍阿片类替代疗法（ORT）的人的可待因的常见来源。我们之前的工作表明，治疗前CACC和口服丁丙诺啡剂量之间没有关系；我们假设CYP2D6活性将部分解释这种断开。将106名CUD参与者与5408名澳大利亚患者的已公布人群样本进行了比较。CUD参与者在进入治疗时的平均年龄为35岁，CUD的平均持续时间为6.1年。可待因的平均剂量为660 mg/天（范围40-2700 mg）。可待因组的平均计算CYP2D6活性评分显著较高（CUD 1.65 + 0.63对流行一代1.39 + 0.65，Wilcoxon W = 347001，第页

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来源期刊

Pharmacogenomics Journal 医学-药学

CiteScore

7.20

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The Pharmacogenomics Journal is a print and electronic journal, which is dedicated to the rapid publication of original research on pharmacogenomics and its clinical applications. Key areas of coverage include: Personalized medicine Effects of genetic variability on drug toxicity and efficacy Identification and functional characterization of polymorphisms relevant to drug action Pharmacodynamic and pharmacokinetic variations and drug efficacy Integration of new developments in the genome project and proteomics into clinical medicine, pharmacology, and therapeutics Clinical applications of genomic science Identification of novel genomic targets for drug development Potential benefits of pharmacogenomics.