ArticlePloS one2013
CYP2D6 genotype dependent oxycodone metabolism in postoperative patients.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.
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Who cites it
33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 79 citations in OpenAlex.
- Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2D6 and opioids (codeine, tramadol and oxycodone).European journal of human genetics : EJHG · 2022Guideline
- Appraisal and development of evidence-based clinical decision support to enable perioperative pharmacogenomic application.The pharmacogenomics journal · 2021Pooled it
- Pharmacogenetic Guided Opioid Therapy Improves Chronic Pain Outcomes and Comorbid Mental Health: A Randomized, Double-Blind, Controlled Study.International journal of molecular sciences · 2023Trial
- Pharmacokinetics and Bioequivalence Evaluation of a New Oxycodone Tamper-Resistant Tablet Administered with an Opioid Antagonist in Patients with Chronic Pain.Clinical drug investigation · 2020Trial
- Population pharmacokinetics and analgesic potency of oxycodone.British journal of clinical pharmacology · 2017Trial
- Effects of aprepitant on the pharmacokinetics of controlled-release oral oxycodone in cancer patients.PloS one · 2014Trial
- CYP2D6 Metabolizer Phenotype and New Persistent Opioid Use After Spine Surgery.Global spine journal · 2026Article
- CYP2D6 gene polymorphisms influence postoperative pain sensitivity and drug response in lung cancer surgery.International journal of clinical and experimental pathology · 2026Article
- Precision Medicine in Astronauts: Principles and Targets in Molecular Assessment.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Pharmacological Mechanisms and Clinical Applications of Oxycodone in Cancer Pain Management: A Narrative Review.Drug design, development and therapy · 2026Review
- Brain Cytochrome P450: Navigating Neurological Health and Metabolic Regulation.Journal of xenobiotics · 2025Review
- Do CYP2D6 genotypes affect oxycodone dose, pharmacokinetics, pain, and adverse effects in cancer?Pharmacogenomics · 2024Article
- Pharmacogenetic landscape of pain management variants among Mediterranean populations.Frontiers in pharmacology · 2024Article
- Hydrocodone, Oxycodone, and Morphine Metabolism and Drug-Drug Interactions.The Journal of pharmacology and experimental therapeutics · 2023Review
- Pharmacogenetic Analysis Enables Optimization of Pain Therapy: A Case Report of Ineffective Oxycodone Therapy.Journal of personalized medicine · 2023Article
- Association ofAnnals of translational medicine · 2022Article
- The Role of Pharmacogenomics in Opioid Prescribing.Current treatment options in oncology · 2022Review
- Patient Perceptions and Potential Utility of Pharmacogenetic Testing in Chronic Pain Management and Opioid Use Disorder in the Camden Opioid Research Initiative.Pharmaceutics · 2022Article
- Impact of genetic variation in CYP2C19, CYP2D6, and CYP3A4 on oxycodone and its metabolites in a large database of clinical urine drug tests.The pharmacogenomics journal · 2022Article
- Risk of Opioid Overdose Associated With Concomitant Use of Oxycodone and Selective Serotonin Reuptake Inhibitors.JAMA network open · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe impact of polymorphic cytochrome P450 CYP2D6 enzyme on oxycodone's metabolism and clinical efficacy is currently being discussed. However, there are only spare data from postoperative settings. The hypothesis of this study is that genotype dependent CYP2D6 activity influences plasma concentrations of oxycodone and its metabolites and impacts analgesic consumption.
methodsPatients received oxycodone 0.05 mg/kg before emerging from anesthesia and patient-controlled analgesia (PCA) for the subsequent 48 postoperative hours. Blood samples were drawn at 30, 90 and 180 minutes after the initial oxycodone dose. Plasma concentrations of oxycodone and its metabolites oxymorphone, noroxycodone and noroxymorphone were analyzed by liquid chromatography-mass spectrometry with electrospray ionization. CYP2D6 genotyping was performed and 121 patients were allocated to the following genotype groups: PM (poor metabolizer: no functionally active CYP2D6 allele), HZ/IM (heterozygous subjects, intermediate metabolizers with decreased CYP2D6 activity), EM (extensive metabolizers, normal CYP2D6 activity) and UM (ultrarapid metabolizers, increased CYP2D6 activity). Primary endpoint was the genotype dependent metabolite ratio of plasma concentrations oxymorphone/oxycodone. Secondary endpoint was the genotype dependent analgesic consumption with calculation of equianalgesic doses compared to the standard non-CYP dependent opioid piritramide.
resultsMetabolism differed between CYP2D6 genotypes. Mean (95%-CI) oxymophone/oxycodone ratios were 0.10 (0.02/0.19), 0.13 (0.11/0.16), 0.18 (0.16/0.20) and 0.28 (0.07/0.49) in PM, HZ/IM, EM and UM, respectively (p = 0.005). Oxycodone consumption up to the 12(th) hour was highest in PM (p = 0.005), resulting in lowest equianalgesic doses of piritramide versus oxycodone for PM (1.6 (1.4/1.8); EM and UM 2.2 (2.1/2.3); p<0.001). Pain scores did not differ between genotypes.
conclusionsIn this postoperative setting, the number of functionally active CYP2D6 alleles had an impact on oxycodone metabolism. The genotype also impacted analgesic consumption, thereby causing variation of equianalgesic doses piritramide : oxycodone. Different analgesic needs by genotypes were met by PCA technology in this postoperative cohort.
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