Evidence map›Paper›PMID 32346827›Full record

ArticleDrugs & aging2020

Prescribed Doses of CYP2D6-Metabolized Drugs and Hemodynamic Responses in Relation to CYP2D6 Genotype Among Older Patients Exposed to Polypharmacy.

Rita Romskaug, Torgeir Bruun Wyller, Jørund Straand, Hege Kersten, Espen Molden

Open access · hybridAbstract read
In one paragraph

Article in Drugs & aging, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact, top 94% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Article
4 · The record

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5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Rita RomskaugInstitute of Clinical Medicine, University of Oslo, Oslo, Norway. ritulf@gmail.com.ORCID 0000-0002-3251-6349
Torgeir Bruun WyllerInstitute of Clinical Medicine, University of Oslo, Oslo, Norway.
Jørund StraandDepartment of General Practice, Institute of Health and Society, University of Oslo, Oslo, Norway.
Hege KerstenDepartment of Pharmacy, University of Oslo, Oslo, Norway.
Espen MoldenDepartment of Pharmacy, University of Oslo, Oslo, Norway.
University of Oslo · NOOslo University Hospital · NO

Funding

Norges Forskningsråd 222033/LAB
6 · The paper itself

Abstract

backgroundMany drugs with dose-dependent effects on hemodynamic variables are metabolized by cytochrome P450 2D6 (CYP2D6). The aim of this study was to compare prescribed dosages and hemodynamic responses of such drugs in relation to pharmacogenetic variability in CYP2D6 metabolism among patients aged ≥ 70 years exposed to polypharmacy. MATERIALS AND

methodsWe included 173 patients with detailed information about drug use. The patients were retrospectively subjected to CYP2D6 genotyping, which comprised the most common variant alleles encoding reduced, absent, or increased CYP2D6 metabolism. In order to compare dosages across different CYP2D6-metabolized drugs, all prescribed daily doses were harmonized to the 'percent of a daily defined dose' (DDD). The mean harmonized DDD was compared between genotype-predicted normal metabolizers (NMs) and patients with reduced or absent CYP2D6 enzyme activity, defined as intermediate or poor metabolizers (IMs/PMs). Blood pressure, pulse, and patient proportions with orthostatism and bradycardia were also compared between genotype subgroups.

resultsThe genotype-predicted phenotype subgroups comprised 79 NMs (45.7%), 75 IMs (43.4%), and 16 PMs (9.2%). There were no differences in dosing of CYP2D6 substrates between NMs and IMs/PMs (p = 0.76). A higher proportion of CYP2D6 IMs/PMs experienced orthostatism (p = 0.03), while there were no significant subgroup differences for the other hemodynamic variables.

conclusionIn this real-life clinical setting of patients aged ≥ 70 years, dosing of CYP2D6 substrates were not adjusted according to genotype-predicted CYP2D6 metabolism. The increased occurrence of orthostatism in patients with reduced/absent CYP2D6 metabolism may indicate that individualized dosing based on genotype has the potential to prevent adverse effects in these vulnerable patients.

Indexed as

GenotypePolypharmacyAgedAllelesBlood PressureCytochrome P-450 CYP2D6Dose-Response Relationship, DrugFemaleHeart RateHemodynamicsHumansMaleMiddle AgedRetrospective StudiesCytochrome P-450 CYP2D6

Identifiers

PMID32346827
PMCPMC7272489
OpenAlexW3018849936

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LicenceCC BY-NC
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Registered trials

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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.