Low risk of the TMPRSS2 inhibitor camostat mesylate and its metabolite GBPA to act as perpetrators of drug-drug interactions.

Johanna Weiss, Gzona Bajraktari-Sylejmani, Walter Emil Haefeli

Open access · greenAbstract read

In one paragraph

Article in Chemico-biological interactions, 2021. 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

0.3field-weighted citation impact, top 43% 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, 3 citations in OpenAlex.

Safety Evaluation and Population Pharmacokinetics of Camostat Mesylate and Its Major Metabolites Using a Phase I Study.Pharmaceutics · 2023
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

3 authors at 1 institution in 1 country.

Johanna WeissDepartment of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany. Electronic address: johanna.weiss@med.uni-heidelberg.de.

Gzona Bajraktari-SylejmaniDepartment of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.

Walter Emil HaefeliDepartment of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.

Heidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Camostat mesylate, a potent inhibitor of the human transmembrane protease, serine 2 (TMPRSS2), is currently under investigation for its effectiveness in COVID-19 patients. For its safe application, the risks of camostat mesylate to induce pharmacokinetic drug-drug interactions with co-administered drugs should be known. We therefore tested in vitro the potential inhibition of important efflux (P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP, ABCG2)), and uptake transporters (organic anion transporting polypeptides OATP1B1, OATP1B3, OATP2B1) by camostat mesylate and its active metabolite 4-(4-guanidinobenzoyloxy)phenylacetic acid (GBPA). Transporter inhibition was evaluated using fluorescent probe substrates in transporter over-expressing cell lines and compared to the respective parental cell lines. Moreover, possible mRNA induction of pharmacokinetically relevant genes regulated by the nuclear pregnane X receptor (PXR) and aryl hydrocarbon receptor (AhR) was analysed in LS180 cells by quantitative real-time PCR. The results of our study for the first time demonstrated that camostat mesylate and GBPA do not relevantly inhibit P-gp, BCRP, OATP1B1 or OATP1B3. Only OATP2B1 was profoundly inhibited by GBPA with an IC

Indexed as

Drug InteractionsATP Binding Cassette Transporter, Subfamily G, Member 2Cell LineCell SurvivalCytochrome P-450 CYP1A1Cytochrome P-450 CYP3AEstersGuanidinesHumansOrganic Anion TransportersPregnane X ReceptorReceptors, Aryl HydrocarbonRNA, MessengerSerine EndopeptidasesSerine Proteinase Inhibitors4-(4-guanidinobenzoyloxy)phenylacetic acidATP Binding Cassette Transporter, Subfamily G, Member 2camostatCytochrome P-450 CYP1A1Cytochrome P-450 CYP3AEstersGuanidinesOrganic Anion TransportersPregnane X ReceptorReceptors, Aryl HydrocarbonRNA, MessengerSerine EndopeptidasesSerine Proteinase InhibitorsSLCO2B1 protein, humanTMPRSS2 protein, humanCamostat mesylateCOVID-19Drug-drug interactionsDrug transportersGBPASARS-CoV-2

Identifiers

PMID33647240

DOI10.1016/j.cbi.2021.109428

PMCPMC9748837

OpenAlexW3135175421

What OpenQuestion holds

Textmetadata

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 OpenQuestion graph.