Evidence map›Paper›PMID 35337152›Full record

ArticlePharmaceuticals (Basel, Switzerland)2022

Factors Influencing the Intracellular Concentrations of the Sofosbuvir Metabolite GS-331007 (in PBMCs) at 30 Days of Therapy.

Jessica Cusato, Lucio Boglione, Amedeo De Nicolò, Gian Paolo Caviglia, Simone Mornese Pinna, Alessia Ciancio, Giulia Troshina, Antonina Smedile, Miriam Antonucci, Valeria Avataneo and 8 more

Open access · goldAbstract read
In one paragraph

Article in Pharmaceuticals (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.6field-weighted citation impact, top 37% 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

0 citing papers in PubMed, 4 citations in OpenAlex.

No citing paper in PubMed yet.

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

18 authors at 3 institutions in 2 countries.

Jessica CusatoDepartment of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy.ORCID 0000-0003-1977-9694
Lucio BoglioneDepartment of Traslational Medicine, University of Eastern Piedmont, 28100 Novara, Italy.
Amedeo De NicolòDepartment of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy.ORCID 0000-0002-5973-9948
Gian Paolo CavigliaDepartment of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy.ORCID 0000-0002-0529-9481
Simone Mornese PinnaDepartment of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy.
Alessia CiancioDepartment of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy.
Giulia TroshinaDepartment of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy.
Antonina SmedileDepartment of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy.
Miriam AntonucciDepartment of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy.ORCID 0000-0002-5344-9659
Valeria AvataneoDepartment of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy.ORCID 0000-0002-4102-5218
Alice PalermitiDepartment of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy.ORCID 0000-0003-0860-280X
Jacopo MulaDepartment of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy.
Alessandra MancaDepartment of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy.ORCID 0000-0002-8540-6709
Giuseppe CaritiDepartment of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy.
Marco CantùLaboratory of Clinical Biochemistry and Pharmacology, Department of Laboratory Medicine EOLAB, Ente Ospedaliero Cantonale, CH-6500 Bellinzona, Switzerland.
Giorgio Maria SaraccoDepartment of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy.ORCID 0000-0001-5310-4143
Giovanni Di PerriDepartment of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy.
Antonio D'AvolioDepartment of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy.ORCID 0000-0002-1321-4126
Ospedale Amedeo di Savoia · ITEnte Ospedaliero Cantonale · CHUniversità degli Studi del Piemonte Orientale “Amedeo Avogadro” · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sofosbuvir (SOF) is an HCV NS5B polymerase inhibitor, and GS-331007 is its major metabolite. The aim of this study was to investigate whether clinical and pharmacological factors could influence GS-331007 intracellular (IC) concentrations in peripheral blood mononuclear cells (PBMCs) associated with a sustained virological response in patients treated with SOF and ribavirin (RBV). Drug levels were analyzed using liquid chromatography at different days of therapy, whereas variants in genes encoding transporters and nuclear factors were investigated using real-time PCR. This study enrolled 245 patients treated with SOF; 245 samples were analyzed for pharmacogenetics and 50 were analyzed for IC pharmacokinetics. The GS-331007 IC concentration at 30 days was associated with its plasma concentration determinate at 30, 60 and 90 days of SOF-therapy and with daclatasvir concentrations at 7 days of therapy. No genetic polymorphism affected IC exposure. In linear multivariate analysis, ledipasvir treatment, baseline albumin and estimated glomerular filtration rate were significant predictors of IC exposure. This study presents data on an IC evaluation in a cohort of patients treated with SOF, also considering pharmacogenetics. These results could be useful for regions where SOF-RBV treatment is considered the standard of care; moreover, they could further deepen the knowledge of IC exposure for similar drugs in the future.

Indexed as

ABCB1ABCG2DAAsHNF4αpharmacokineticssingle nucleotide polymorphism

Identifiers

PMID35337152
PMCPMC8953593
OpenAlexW4220817256

What OpenQuestion holds

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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.