Evidence map›Paper›PMID 39444174›Full record

ArticleCPT: pharmacometrics & systems pharmacology2025

Establishing a physiologically based pharmacokinetic framework for aldehyde oxidase and dual aldehyde oxidase-CYP substrates.

Nihan Izat, Jayaprakasam Bolleddula, Pasquale Carione, Leticia Huertas Valentin, Robert S Jones, Priyanka Kulkarni, Darren Moss, Vincent C Peterkin, Dan-Dan Tian, Andrea Treyer and 6 more

Abstract read
In one paragraph

Article in CPT: pharmacometrics & systems 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

16 authors.

Nihan IzatCentre for Applied Pharmacokinetic Research, The University of Manchester, Manchester, UK.ORCID 0000-0001-7378-9100
Jayaprakasam BolleddulaEMD Serono Research & Development Institute, Inc., Billerica, Massachusetts, USA.
Pasquale CarioneGenentech, Inc., South San Francisco, California, USA.
Leticia Huertas ValentinGSK R&D, Tres Cantos, Madrid, Spain.
Robert S JonesGenentech, Inc., South San Francisco, California, USA.ORCID 0000-0002-5283-8070
Priyanka KulkarniTakeda Pharmaceuticals Limited, Cambridge, Massachusetts, USA.
Darren MossJanssen Pharmaceutical Companies of Johnson & Johnson, Beerse, Belgium.
Vincent C PeterkinAbbVie Inc., North Chicago, Illinois, USA.
Dan-Dan TianEli Lilly and Company, Indianapolis, Indiana, USA.
Andrea TreyerJanssen Pharmaceutical Companies of Johnson & Johnson, Beerse, Belgium.
Karthik VenkatakrishnanEMD Serono Research & Development Institute, Inc., Billerica, Massachusetts, USA.
Michael A ZientekTakeda Pharmaceuticals Limited, San Diego, California, USA.
Jill BarberCentre for Applied Pharmacokinetic Research, The University of Manchester, Manchester, UK.
J Brian HoustonCentre for Applied Pharmacokinetic Research, The University of Manchester, Manchester, UK.
Aleksandra GaletinCentre for Applied Pharmacokinetic Research, The University of Manchester, Manchester, UK.ORCID 0000-0002-3933-5217
Daniel ScotcherCentre for Applied Pharmacokinetic Research, The University of Manchester, Manchester, UK.ORCID 0000-0001-9144-3824

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aldehyde oxidase (AO) contributes to the clearance of many approved and investigational small molecule drugs, which are often dual substrates of AO and drug-metabolizing enzymes such as cytochrome P450s (CYPs). As such, the lack of established framework for quantitative translation of the clinical pharmacologic correlates of AO-mediated clearance represents an unmet need. This study aimed to evaluate the utility of physiologically based pharmacokinetic (PBPK) modeling in the development of AO and dual AO-CYP substrates. PBPK models were developed for capmatinib, idelalisib, lenvatinib, zaleplon, ziprasidone, and zoniporide, incorporating in vitro functional data from human liver subcellular fractions and human hepatocytes. Prediction of metabolic elimination with/without the additional empirical scaling factors (ESFs) was assessed. Clinical pharmacokinetics, human mass balance, and drug-drug interaction (DDI) studies with CYP3A4 modulators, where available, were used to refine/verify the models. Due to the lack of clinically significant AO-DDIs with known AO inhibitors, the fraction metabolized by AO (fm

Indexed as

Aldehyde OxidaseDrug InteractionsModels, BiologicalCytochrome P-450 CYP3ACytochrome P-450 Enzyme SystemHepatocytesHumansLiverAldehyde OxidaseCytochrome P-450 CYP3ACytochrome P-450 Enzyme System

Identifiers

PMID39444174
PMCPMC11706420

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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.