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. 2023 Nov;23(6):195-200.
doi: 10.1038/s41397-023-00319-6. Epub 2023 Nov 9.

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

Mark R C Daglish  1   2   3 , Sarah R Reilly  4 , Sam Mostafa  5   6 , Cameron Edwards  4 , Thomas M O'Gorman  4 , Jeremy S Hayllar  4
Affiliations

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

Mark R C Daglish et al. Pharmacogenomics J. 2023 Nov.

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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Conflict of interest statement

MRCD has received honoraria from Indivior & Camurus for unrelated work. JSH has received honoraria from Camurus and Indivior for unrelated work, donated to a humanitarian charity. SM is an employee and shareholder of myDNA Inc, a pharmacogenomic testing and interpretation company. The research was supported by a grant to SRR from The Prince Charles Hospital, Common Good Foundation.

Figures

Fig. 1
Fig. 1. Proportions in CPIC phenotype groups.
Filled bars represent observed proportions. Error bars represent predicted proportions from ordinal logistic regression with 95% CI. General general population, Codeine codeine use disorder group, PM poor metaboliser, IM intermediate metaboliser, NM normal metaboliser, UM ultrarapid metabolizer.
Fig. 2
Fig. 2. Codeine doses across CYP2D6 phenotypes.
PM poor metaboliser, IM intermediate metaboliser, NM normal metaboliser, UM ultrarapid metabolizer.
Fig. 3
Fig. 3. Relationship between stabilisation buprenorphine doses and maximum codeine dose.
PM poor metaboliser, IM intermediate metaboliser, NM normal metaboliser, UM ultrarapid metabolizer.
Fig. 4
Fig. 4. Interaction between codeine and CYP2D6 phenotype on stabilisation dose of buprenorphine.
PM poor metaboliser, IM intermediate metaboliser, NM normal metaboliser, UM ultrarapid metabolizer.
See this image and copyright information in PMC

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