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

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

Aaron K Wong  1   2   3 , Sara Vogrin  4 , Pal Klepstad  5 , Justin Rubio  6 , Brian Le  1   2 , Jennifer Philip  1   2   3   7 , Andrew A Somogyi  8
Affiliations
Multicenter Study

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

Aaron K Wong et al. Pharmacogenomics. 2024.

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.

Keywords: Opioid; advanced cancer; analgesics; palliative care; pharmacogenetics.

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Conflict of interest statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Figures

Figure 1.
Figure 1.
Box and whisker plots of median plasma concentrations (ng/ml) of (a) oxycodone, (b) oxymorphone, and (c) oxymorphone/oxycodone ratio for CYP2D6 normal metabolisers compared to intermediate and Poor metabolisers.
See this image and copyright information in PMC

References

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