Evidence mapPaperPMID 35455642Full record

ArticleJournal of personalized medicine2022

Impact of the Genotype and Phenotype of CYP3A and P-gp on the Apixaban and Rivaroxaban Exposure in a Real-World Setting.

Camille Lenoir, Jean Terrier, Yvonne Gloor, Pauline Gosselin, Youssef Daali, Christophe Combescure, Jules Alexandre Desmeules, Caroline Flora Samer, Jean-Luc Reny, Victoria Rollason

Open access · goldAbstract read
In one paragraph

Article in Journal of personalized medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 2 pooled it
4.4field-weighted citation impact, top 4% 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

18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
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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 2 institutions in 1 country.

Camille LenoirDepartment of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, 1205 Geneva, Switzerland.ORCID 0000-0001-6506-8629
Jean TerrierDepartment of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, 1205 Geneva, Switzerland.
Yvonne GloorDepartment of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, 1205 Geneva, Switzerland.
Pauline GosselinDepartment of Medicine, Division of General Internal Medicine, Geneva University Hospitals, 1205 Geneva, Switzerland.
Youssef DaaliDepartment of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, 1205 Geneva, Switzerland.ORCID 0000-0002-8391-9383
Christophe CombescureFaculty of Medicine, University of Geneva, 1206 Geneva, Switzerland.
Jules Alexandre DesmeulesDepartment of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, 1205 Geneva, Switzerland.
Caroline Flora SamerDepartment of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, 1205 Geneva, Switzerland.
Jean-Luc RenyDepartment of Medicine, Division of General Internal Medicine, Geneva University Hospitals, 1205 Geneva, Switzerland.
Victoria RollasonDepartment of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, 1205 Geneva, Switzerland.ORCID 0000-0002-8073-6610
University of Geneva · CHUniversity Hospital of Geneva · CH

Funding

Geneva University Hospitals 19-2014-II
6 · The paper itself

Abstract

Apixaban and rivaroxaban are the two most prescribed direct factor Xa inhibitors. With the increased use of DOACs in real-world settings, safety and efficacy concerns have emerged, particularly regarding their concomitant use with other drugs. Increasing evidence highlights drug−drug interactions with CYP3A/P-gp modulators leading to adverse events. However, current recommendations for dose adjustment do not consider CYP3A/P-gp genotype and phenotype. We aimed to determine their impact on apixaban and rivaroxaban blood exposure. Three-hundred hospitalized patients were included. CYP3A and P-gp phenotypic activities were assessed by the metabolic ratio of midazolam and AUC0−6h of fexofenadine, respectively. Relevant CYP3A and ABCB1 genetic polymorphisms were also tested. Capillary blood samples collected at four time-points after apixaban or rivaroxaban administration allowed the calculation of pharmacokinetic parameters. According to the developed multivariable linear regression models, P-gp activity (p < 0.001) and creatinine clearance (CrCl) (p = 0.01) significantly affected apixaban AUC0−6h. P-gp activity (p < 0.001) also significantly impacted rivaroxaban AUC0−6h. The phenotypic switch (from normal to poor metabolizer) of P-gp led to an increase of apixaban and rivaroxaban AUC0−6h by 16% and 25%, respectively, equivalent to a decrease of 38 mL/min in CrCl according to the apixaban model. CYP3A phenotype and tested SNPs of CYP3A/P-gp had no significant impact. In conclusion, P-gp phenotypic activity, rather than known CYP3A/P-gp polymorphisms, could be relevant for dose adjustment.

Indexed as

DOACsmetabolismpersonalized medicinepharmacogenomicsphenotype

Identifiers

PMID35455642
PMCPMC9028714
OpenAlexW4220964805

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.