Evidence map›Paper›PMID 29882961›Full record

Trial reportClinical pharmacology and therapeutics2018

CYP2D6 Genotype Phenotype Discordance Due to Drug-Drug Interaction.

Andrew A Monte, Kelsey West, Kyle T McDaniel, Hania K Flaten, Jessica Saben, Shelby Shelton, Farah Abdelmawla, Lane R Bushman, Kayla Williamson, Diana Abbott and 1 more

Abstract readPragmatic Clinical Trial
In one paragraph

Trial report in Clinical pharmacology and therapeutics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
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

9 citing papers in PubMed.

  1. Article
  2. Article
  3. CYP2D6 pharmacogenetics and phenoconversion in personalized medicine.Expert opinion on drug metabolism & toxicology · 2022
    Review
  4. Article
  5. Review
  6. ClinicalCancers · 2021
    Review
  7. Article
  8. Article
  9. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Andrew A MonteDepartment of Emergency Medicine & Colorado Center for Personalized Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
Kelsey WestDepartment of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA.
Kyle T McDanielDepartment of Emergency Medicine & Colorado Center for Personalized Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
Hania K FlatenDepartment of Emergency Medicine & Colorado Center for Personalized Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
Jessica SabenDepartment of Emergency Medicine & Colorado Center for Personalized Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
Shelby SheltonDepartment of Emergency Medicine & Colorado Center for Personalized Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
Farah AbdelmawlaDepartment of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA.
Lane R BushmanDepartment of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA.
Kayla WilliamsonDepartment of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado, USA.
Diana AbbottDepartment of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado, USA.
Peter L AndersonDepartment of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA.

Funding

Colorado Clinical and Translational Sciences InstituteUL1TR001082 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2013 to 2017
$48.0M
PERSONALIZING EMERGENCY/ACUTE THERAPEUTICS UTILIZING SYSTEMS BIOLOGY (PEGASUS)R35GM124939 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI MONTE, ANDREW ALBERT · 2017 to 2021
$2.1M
An Integrated Approach to Personalized MedicineK23GM110516 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI MONTE, ANDREW ALBERT · 2014 to 2016
$588k
NCATS NIH HHS UL1 TR001082NIGMS NIH HHS K23 GM110516NIGMS NIH HHS R35 GM124939
6 · The paper itself

Abstract

Drug-drug interactions have been demonstrated to alter cytochrome 2D6 (CYP2D6) enzyme phenotype due to inhibitor ingestion, although it is unclear how substrate interactions affect phenotype. This was a pragmatic clinical trial examining the kinetics of a CYP2D6 enzyme probe drug with and without CYP2D6-dependent substrates. Patients were enrolled into an inpatient study unit, and orally administered a 2 mg microdose of dextromethorphan (DM) to probe enzyme activity with and without CYP2D6-dependent drug-drug interactions. Thirty-nine subjects were enrolled in this trial. Twelve subjects were on no CYP2D6-dependent drugs and 27 were on one or more CYP2D6-dependent drugs. There were 1 poor metabolizer, 5 intermediate metabolizers, 31 normal metabolizers, and 2 ultra-rapid metabolizers. Those with co-ingestion of another CYP2D6-dependent drug were 9.49 (95% confidence interval (CI): 1.54-186.41; P = 0.01) times more likely to have genotype-phenotype discordance based upon the 3 hours dextrophan/dextromethorphan (DX/DM) ratio. CYP2D6 substrate co-ingestions can cause genotype-phenotype discordance.

Indexed as

Pharmacogenomic VariantsAdministration, OralAgedColoradoCytochrome P-450 CYP2D6Cytochrome P-450 CYP2D6 InhibitorsDextromethorphanDrug InteractionsFemaleGenotypeHumansMaleMiddle AgedModels, BiologicalPhenotypeProspective StudiesCytochrome P-450 CYP2D6Cytochrome P-450 CYP2D6 InhibitorsDextromethorphan

Identifiers

PMID29882961
PMCPMC6197912

What OpenQuestion holds

Textmetadata
LicenceTDM
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.