Evidence map›Paper›PMID 37415001›Full record

ArticleInvestigational new drugs2023

Assessment of the potential of the MET inhibitor tepotinib to affect the pharmacokinetics of CYP3A4 and P-gp substrates.

Özkan Yalkinoglu, Andreas Becker, Axel Krebs-Brown, Claudia Vetter, Christian Lüpfert, Dominique Perrin, Jürgen Heuer, Herlind Biedert, Stefan Hirt, Afrim Bytyqi and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Investigational new drugs, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Review
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

12 authors at 2 institutions in 1 country.

Özkan YalkinogluClinical Pharmacology, Quantitative Pharmacology, the healthcare business of Merck KGaA, Darmstadt, Germany.
Andreas BeckerClinical Pharmacology, Quantitative Pharmacology, the healthcare business of Merck KGaA, Darmstadt, Germany.
Axel Krebs-BrownGlobal Biostatistics, Epidemiology and Medical Writing, the healthcare business of Merck KGaA, Darmstadt, Germany.
Claudia VetterClinical Pharmacology, Quantitative Pharmacology, the healthcare business of Merck KGaA, Darmstadt, Germany.
Christian LüpfertClinical Pharmacology, Quantitative Pharmacology, the healthcare business of Merck KGaA, Darmstadt, Germany.
Dominique PerrinNCE DMPK, Discovery and Development Technologies, the healthcare business of Merck KGaA, Darmstadt, Germany.
Jürgen HeuerClinical Services, Nuvisan GmbH, Neu-Ulm, Germany.
Herlind BiedertLC/MS Bioanalysis, Nuvisan GmbH, Neu-Ulm, Germany.
Stefan HirtLC/MS Bioanalysis, Nuvisan GmbH, Neu-Ulm, Germany.
Afrim BytyqiClinical Pharmacology, Quantitative Pharmacology, the healthcare business of Merck KGaA, Darmstadt, Germany.
Angelika BachmannClinical Pharmacology, Quantitative Pharmacology, the healthcare business of Merck KGaA, Darmstadt, Germany.
Rainer StrotmannClinical Pharmacology, Quantitative Pharmacology, the healthcare business of Merck KGaA, Darmstadt, Germany. Rainer.Strotmann@emdserono.com.
Merck (Germany) · DENuvisan (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tepotinib is a highly selective, potent, mesenchymal-epithelial transition factor (MET) inhibitor, approved for the treatment of non-small cell lung cancer harboring MET exon 14 skipping alterations. The aims of this work were to investigate the potential for drug-drug interactions via cytochrome P450 (CYP) 3A4/5 or P-glycoprotein (P-gp) inhibition. In vitro studies were conducted in human liver microsomes, human hepatocyte cultures and Caco-2 cell monolayers to investigate whether tepotinib or its major metabolite (MSC2571109A) inhibited or induced CYP3A4/5 or inhibited P-gp. Two clinical studies were conducted to investigate the effect of multiple dose tepotinib (500 mg once daily orally) on the single dose pharmacokinetics of a sensitive CYP3A4 substrate (midazolam 7.5 mg orally) and a P-gp substrate (dabigatran etexilate 75 mg orally) in healthy participants. Tepotinib and MSC2571109A showed little evidence of direct or time-dependent CYP3A4/5 inhibition (IC

Indexed as

Carcinoma, Non-Small-Cell LungLung NeoplasmsATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1Caco-2 CellsCytochrome P-450 CYP3ACytochrome P-450 Enzyme SystemDabigatranDrug InteractionsHumansMidazolamPiperidinesPyridazinesPyrimidinesATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1CYP3A4 protein, humanCytochrome P-450 CYP3ACytochrome P-450 Enzyme SystemDabigatranMidazolamPiperidinesPyridazinesPyrimidinestepotinibCYP3A4Drug-drug interactionsMET inhibitorP-glycoproteinTepotinib

Identifiers

PMID37415001
PMCPMC10447267
OpenAlexW4383314199

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.