Evidence map›Paper›PMID 40195783›Full record

ArticleJournal of clinical pharmacology2025

Physiologically Based Pharmacokinetic (PBPK) Model to Predict the Magnitude of Drug-Drug Interaction Between Fezolinetant and CYP1A2 Inhibitors.

Mary P Choules, Yukio Otsuka, Jace C Nielsen, Megumi Iwai, Peter L Bonate

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of clinical pharmacology, 2025. 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
–field-weighted citation impact
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.

  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

5 authors.

Mary P ChoulesAstellas Pharma, Inc., Northbrook, IL, USA.ORCID 0000-0003-1771-3245
Yukio OtsukaAstellas Pharma, Inc., Tokyo, Japan.
Jace C NielsenAstellas Pharma, Inc., Northbrook, IL, USA.ORCID 0009-0009-4950-7957
Megumi IwaiAstellas Pharma, Inc., Tokyo, Japan.
Peter L BonateAstellas Pharma, Inc., Northbrook, IL, USA.

Funding

Astellas Pharma Global DevelopmentAstellas Pharma, Inc
6 · The paper itself

Abstract

Fezolinetant is a non-hormonal, selective neurokinin 3 receptor antagonist approved in multiple countries including the United States, in Europe, and in Asia for the treatment of moderate to severe vasomotor symptoms in menopausal women. Fezolinetant is primarily metabolized by CYP1A2 and was found to be a sensitive substrate for CYP1A2 metabolism based on a clinical DDI study with strong CYP1A2 inhibitor, fluvoxamine. Therefore, coadministration with CYP1A2 inhibitors or inducers (such as smoking) could lead to changes in fezolinetant exposure. A physiological-based pharmacokinetic (PBPK) model was built for fezolinetant using the Simcyp simulator software with in vitro and in vivo data. The final verified model was used to predict fezolinetant exposure following coadministration with mexiletine (moderate CYP1A2 inhibitor), ciprofloxacin (moderate CYP1A2 inhibitor), and cimetidine (weak CYP1A2 inhibitor). Depending on the dosing regimen of the inhibitor and the meal status, coadministration with a weak CYP1A2 inhibitor, such as cimetidine, was predicted to increase fezolinetant C

Indexed as

Cytochrome P-450 CYP1A2 InhibitorsModels, BiologicalAdultCimetidineCytochrome P-450 CYP1A2Drug InteractionsFemaleHumansMaleMiddle AgedCimetidineCYP1A2 protein, humanCytochrome P-450 CYP1A2Cytochrome P-450 CYP1A2 Inhibitorsdrug–drug interaction (DDI)fezolinetantphysiological‐based pharmacokinetics (PBPK)Simcypwomen's health

Identifiers

PMID40195783
PMCPMC12397715

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.