Evidence map›Paper›PMID 37864393›Full record

ArticleBritish journal of clinical pharmacology2024

Effect of isotretinoin on CYP2D6 and CYP3A activity in patients with severe acne.

Yuqian Zhao, Jay C Vary, Aprajita S Yadav, Lindsay C Czuba, Sara Shum, Jeffrey LaFrance, Weize Huang, Nina Isoherranen, Mary F Hebert

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in British journal of clinical pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03076021 (Effects of Isotretinoin on CYP2D6 Activity), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.3field-weighted citation impact, top 35% 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.

NCT03076021 phase4completednot on this map

Effects of Isotretinoin on CYP2D6 Activity

TypeinterventionalSponsorUniversity of WashingtonRan2016 to 2023Enrolled33ConditionsCYP2D6 PolymorphismArmsIsotretinoin, dextromethorphan
3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. Article
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

9 authors at 1 institution in 1 country.

Yuqian ZhaoDepartment of Pharmaceutics, University of Washington, School of Pharmacy, Seattle, Washington, USA.ORCID 0009-0002-8768-673X
Jay C VaryDepartment of Medicine, Division of Dermatology, University of Washington, School of Medicine, Seattle, Washington, USA.
Aprajita S YadavDepartment of Pharmaceutics, University of Washington, School of Pharmacy, Seattle, Washington, USA.ORCID 0000-0002-4181-7522
Lindsay C CzubaDepartment of Pharmaceutics, University of Washington, School of Pharmacy, Seattle, Washington, USA.
Sara ShumDepartment of Pharmaceutics, University of Washington, School of Pharmacy, Seattle, Washington, USA.
Jeffrey LaFranceDepartment of Pharmaceutics, University of Washington, School of Pharmacy, Seattle, Washington, USA.
Weize HuangDepartment of Pharmaceutics, University of Washington, School of Pharmacy, Seattle, Washington, USA.
Nina IsoherranenDepartment of Pharmaceutics, University of Washington, School of Pharmacy, Seattle, Washington, USA.
Mary F HebertDepartment of Pharmacy, University of Washington, School of Pharmacy, Seattle, Washington, USA.ORCID 0000-0002-2530-8189
University of Washington · US

Funding

Pharmacological Sciences SupplementT32GM007750 · NIGMS · UNIVERSITY OF WASHINGTON · PI ATKINS, WILLIAM M · 1985 to 2023
$12.6M
Understanding Fetal Exposure to Cannabinoids Through In Vitro and In Vivo StudiesP01DA032507 · NIDA · UNIVERSITY OF WASHINGTON · PI UNADKAT, JASHVANT D · 2013 to 2023
$12.4M
Diabetes, Obesity and Metabolism Training ProgramT32DK007247 · NIDDK · UNIVERSITY OF WASHINGTON · PI GREGORY J MORTON, KRISTINA Marie UTZSCHNEIDER · 1986 to 2026
$10.0M
NRSA Training CoreTL1TR002318 · NCATS · UNIVERSITY OF WASHINGTON · PI Megan Moore · 2017 to 2026
$8.4M
Effects of Retinoids on CYP2D6 Activity and Variability in Special PopulationsR01GM124264 · NIGMS · UNIVERSITY OF WASHINGTON · PI HEBERT, MARY F · 2017 to 2020
$2.3M
NCATS NIH HHS TL1 TR002318NIDA NIH HHS P01 DA032507NIDDK NIH HHS T32 DK007247NIGMS NIH HHS P01DA032507NIGMS NIH HHS R01 GM124264NIGMS NIH HHS R01GM124264NIGMS NIH HHS T32 GM007750NIGMS NIH HHS T32GM007750
6 · The paper itself

Abstract

aimsPreviously, retinoids have decreased CYP2D6 mRNA expression in vitro and induced CYP3A4 in vitro and in vivo. This study aimed to determine whether isotretinoin administration changes CYP2D6 and CYP3A activities in patients with severe acne.

methodsThirty-three patients (22 females and 11 males, 23.5 ± 6.0 years old) expected to receive isotretinoin treatment completed the study. All participants were genotyped for CYP2D6 and CYP3A5. Participants received dextromethorphan (DM) 30 mg orally as a dual-probe substrate of CYP2D6 and CYP3A activity at two study timepoints: pre-isotretinoin treatment and with isotretinoin for at least 1 week. The concentrations of isotretinoin, DM and their metabolites were measured in 2-h postdose plasma samples and in cumulative 0-4-h urine collections using liquid chromatography-mass spectrometry.

resultsIn CYP2D6 extensive metabolizers, the urinary dextrorphan (DX)/DM metabolic ratio (MR) (CYP2D6 activity marker) was numerically, but not significantly, lower with isotretinoin administration compared to pre-isotretinoin (geometric mean ratio [GMR] [90% confidence interval (CI)] 0.78 [0.55, 1.11]). The urinary 3-hydroxymorphinan (3HM)/DX MR (CYP3A activity marker) was increased (GMR 1.18 [1.03, 1.35]) and the urinary DX-O-glucuronide/DX MR (proposed UGT2B marker) was increased (GMR 1.22 [1.06, 1.39]) with isotretinoin administration compared to pre-isotretinoin.

conclusionsAdministration of isotretinoin did not significantly reduce CYP2D6 activity in extensive metabolizers, suggesting that the predicted downregulation of CYP2D6 based on in vitro data does not translate into humans. We observed a modest increase in CYP3A activity (predominantly CYP3A4) with isotretinoin treatment. The data also suggest that DX glucuronidation is increased following isotretinoin administration.

Indexed as

Acne VulgarisCytochrome P-450 CYP2D6AdolescentAdultCytochrome P-450 CYP3ADextromethorphanFemaleHumansIsotretinoinMalePhenotypeYoung AdultCytochrome P-450 CYP2D6Cytochrome P-450 CYP3ADextromethorphanIsotretinoinCYP2D6CYP3AdextromethorphanisotretinoinretinoidsUGT2B

Identifiers

PMID37864393
PMCPMC10922942
OpenAlexW4387840681

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.