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Importance of cytochrome 3A4 and 2D6-mediated drug–drug interactions in oxycodone consumption among older adults hospitalized for hip fracture: a cross-sectional study

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Abstract

Hip fracture is a common injury and represents a major health problem with an increasing incidence. In older adults, opioids such as oxycodone are often preferred to other analgesics such as tramadol because of a lower risk of delirium. Different parameters, such as inhibition of cytochrome P450 (CYP450) 2D6 and/or 3A4, can potentially lead to pharmacokinetic variations of oxycodone representing a risk of adverse drugs effects or lack of drug response. There is a risk of drug–drug interactions involving CYP450 in older adults due to the high prevalence of polypharmacy. This study sought to identify patient characteristics that influence oxycodone administration. A single-center observational study included 355 patients with a hip fracture hospitalized in a geriatric postoperative unit. Composite endpoint based on form, duration, and timing to intake separated patients into three groups: "no oxycodone", "low oxycodone ", and "high oxycodone ". CYP450 interactions were studied based on a composite variable defining the most involved CYP450 pathways between CYP2D6 and CYP3A4. CYP450 interactions with CYP2D6 pathway involved were associated with the risk of “high oxycodone” [odds ratio adjusted on age and the type of hip fracture (OR*) 4.52, 95% confidence interval (CI) 1.39–16.83, p = 0.02)], as well as serum albumin levels (OR* 1.09, 95% CI 1.02–1.17, p = 0.01). Cognitive impairment was negatively associated with the risk of “high oxycodone” (OR* 0.38, 95% CI 0.18–0.77, p = 0.02). This study showed an association between CYP2D6 interactions and higher oxycodone consumption indirectly reflecting the existence of uncontrolled postoperative pain.

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Data availability

The data presented in this study are available on request from the corresponding author.

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Acknowledgements

The authors gratefully acknowledge the implication of the staff of the geriatric perioperative unit of the Ambroise Paré Hospital (AP-HP, Boulogne-Billancourt) in the development of research projects to improve the management of patients.

Funding

This research received no external funding.

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Authors and Affiliations

  1. Department of Geriatrics, APHP, GHU Paris-Saclay University, Ambroise Paré Hospital, Boulogne-Billancourt, France

    Théodore Decaix, Luca Royer, Laurent Teillet, Cyril Sellier & Marion Pépin

  2. CNRS, CiTCoM, Paris-Cité University, 75006, Paris, France

    Théodore Decaix & Olivier Laprévote

  3. Epidemiology and Public Health Department, AP-HP, GHU Paris-Saclay University, Raymond Poincaré Hospital, Garches, France

    Sylvain Gautier

  4. Primary Care and Prevention Team, UVSQ, Inserm U1018, CESP, Paris-Saclay University, Villejuif, France

    Sylvain Gautier

  5. Department of Biochemistry, APHP, GHU Paris-Cité University, European Georges Pompidou Hospital, Paris, France

    Olivier Laprévote

  6. Department of Pharmacy, APHP, GHU Paris-Saclay University, Ambroise Paré Hospital, Boulogne-Billancourt, France

    Thomas Tritz

  7. Hematology Laboratory, APHP, Hospital Group Lariboisière-Fernand Widal, Paris-Cité University, Paris, France

    Virginie Siguret

  8. Therapeutic Innovations in Hemostasis, Inserm UMR-S 1140, Paris-Cité University, Paris, France

    Virginie Siguret

  9. Clinical Epidemiology, UVSQ, Inserm U1018, CESP, Paris-Saclay University, Villejuif, France

    Marion Pépin

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  1. Théodore Decaix
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Contributions

Conceptualization, TD, SG, and MP; methodology, TD, SG, and MP; software, TD, SG; validation, TD, SG; formal analysis, TD, SG; investigation, TD, LR, CS; resources, CS, LT, MP; data curation, CS; writing—original draft preparation, TD; writing—review and editing, TD, SG, OL, TT, CS, VS, and MP; visualization, TD; supervision, MP; project administration, MP. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Théodore Decaix.

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The authors declare no conflict of interest.

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The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Paris-Saclay University (CER-Paris-Saclay-2022-047).

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No subjects involved in this study objected to the retrospective processing of their data.

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Decaix, T., Gautier, S., Royer, L. et al. Importance of cytochrome 3A4 and 2D6-mediated drug–drug interactions in oxycodone consumption among older adults hospitalized for hip fracture: a cross-sectional study. Aging Clin Exp Res 35, 2471–2481 (2023). https://doi.org/10.1007/s40520-023-02569-7

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