Evidence map›Paper›PMID 20590588›Full record

Trial reportBritish journal of pharmacology2010

Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety.

C F Samer, Y Daali, M Wagner, G Hopfgartner, C B Eap, M C Rebsamen, M F Rossier, D Hochstrasser, P Dayer, J A Desmeules

Open access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in British journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 7 pooled it
19.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

73 citing papers in PubMed, 7 syntheses or guidelines pooled it, 198 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Guideline
  4. Pooled it
  5. Guideline
  6. Guideline
  7. Guideline
  8. Trial
  9. Trial
  10. Population pharmacokinetics and analgesic potency of oxycodone.British journal of clinical pharmacology · 2017
    Trial
  11. Trial
  12. Trial
  13. Article
  14. Review
  15. Article
  16. Analgesic therapy failure in aPain reports · 2025
    Article
  17. Article
  18. Article
  19. Hydrocodone, Oxycodone, and Morphine Metabolism and Drug-Drug Interactions.The Journal of pharmacology and experimental therapeutics · 2023
    Review
  20. Review

13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

C F SamerClinical Pharmacology and Toxicology and Multidisciplinary Pain Centre, Department of Anaesthesiology, Pharmacology and Intensive Care, Geneva University Hospitals, Geneva, Switzerland. Caroline.Samer@hcuge.ch
Y Daali
M Wagner
G Hopfgartner
C B Eap
M C Rebsamen
M F Rossier
D Hochstrasser
P Dayer
J A Desmeules
University of Geneva · CHSwiss Centre for Applied Human ToxicologyUniversity Hospital of Geneva · CHUniversity of Lausanne · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeThe major drug-metabolizing enzymes for the oxidation of oxycodone are CYP2D6 and CYP3A. A high interindividual variability in the activity of these enzymes because of genetic polymorphisms and/or drug-drug interactions is well established. The possible role of an active metabolite in the pharmacodynamics of oxycodone has been questioned and the importance of CYP3A-mediated effects on the pharmacokinetics and pharmacodynamics of oxycodone has been poorly explored. EXPERIMENTAL APPROACH: We conducted a randomized crossover (five arms) double-blind placebo-controlled study in 10 healthy volunteers genotyped for CYP2D6. Oral oxycodone (0.2 mg x kg(-1)) was given alone or after inhibition of CYP2D6 (with quinidine) and/or of CYP3A (with ketoconazole). Experimental pain (cold pressor test, electrical stimulation, thermode), pupil size, psychomotor effects and toxicity were assessed. KEY

resultsCYP2D6 activity was correlated with oxycodone experimental pain assessment. CYP2D6 ultra-rapid metabolizers experienced increased pharmacodynamic effects, whereas cold pressor test and pupil size were unchanged in CYP2D6 poor metabolizers, relative to extensive metabolizers. CYP2D6 blockade reduced subjective pain threshold (SPT) for oxycodone by 30% and the response was similar to placebo. CYP3A4 blockade had a major effect on all pharmacodynamic assessments and SPT increased by 15%. Oxymorphone C(max) was correlated with SPT assessment (rho(S)= 0.7) and the only independent positive predictor of SPT. Side-effects were observed after CYP3A4 blockade and/or in CYP2D6 ultra-rapid metabolizers. CONCLUSIONS AND IMPLICATIONS: The modulation of CYP2D6 and CYP3A activities had clear effects on oxycodone pharmacodynamics and these effects were dependent on CYP2D6 genetic polymorphism.

Indexed as

Polymorphism, GeneticAdultAnalgesics, OpioidCross-Over StudiesCytochrome P-450 CYP2D6Cytochrome P-450 CYP2D6 InhibitorsCytochrome P-450 CYP3ACytochrome P-450 CYP3A InhibitorsDouble-Blind MethodDrug InteractionsEnzyme InhibitorsGenotypeHumansMaleMetabolic Detoxication, Phase IMiddle AgedAnalgesics, OpioidCYP3A protein, humanCytochrome P-450 CYP2D6Cytochrome P-450 CYP2D6 InhibitorsCytochrome P-450 CYP3ACytochrome P-450 CYP3A InhibitorsEnzyme InhibitorsOxycodoneOxymorphone

Identifiers

PMID20590588
PMCPMC2935998
OpenAlexW2013235742

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.