Evidence map›Paper›PMID 35390174›Full record

ReviewClinical pharmacology and therapeutics2022

Regulation of Drug Transport Proteins-From Mechanisms to Clinical Impact: A White Paper on Behalf of the International Transporter Consortium.

Kim L R Brouwer, Raymond Evers, Elizabeth Hayden, Shuiying Hu, Cindy Yanfei Li, Henriette E Meyer Zu Schwabedissen, Sibylle Neuhoff, Stefan Oswald, Micheline Piquette-Miller, Chitra Saran and 4 more

Open access · greenAbstract readReviewConsensus Statement
In one paragraph

Review in Clinical pharmacology and therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 1 pooled it
6.1field-weighted citation impact, top 3% 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

44 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.

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  10. Effect of proinflammatory cytokines on intestinal drug transporters in human enteroid monolayers.Drug metabolism and disposition: the biological fate of chemicals · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 12 institutions in 7 countries.

Kim L R BrouwerDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.ORCID 0000-0003-1945-4929
Raymond EversPreclinical Sciences and Translational Safety, Johnson & Johnson, Janssen Pharmaceuticals, Spring House, Pennsylvania, USA.
Elizabeth HaydenDepartment of Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, USA.ORCID 0000-0002-4730-3557
Shuiying HuCollege of Pharmacy, The Ohio State University, Columbus, Ohio, USA.ORCID 0000-0002-9806-7734
Cindy Yanfei LiPKDM, Amgen Inc., South San Francisco, California, USA.
Henriette E Meyer Zu SchwabedissenBiopharmacy, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.ORCID 0000-0003-0458-4579
Sibylle NeuhoffCertara UK Ltd., Simcyp Division, Sheffield, UK.ORCID 0000-0001-8809-1960
Stefan OswaldInstitute of Pharmacology and Toxicology, Rostock University Medical Center, Rostock, Germany.ORCID 0000-0001-6269-4368
Micheline Piquette-MillerLeslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0002-3847-8224
Chitra SaranDepartment of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.ORCID 0000-0001-5311-1917
Noora SjöstedtDivision of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.ORCID 0000-0001-6960-7757
Jason A SprowlDepartment of Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, USA.ORCID 0000-0003-2573-2518
Simone H StahlCVRM Safety, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge, UK.ORCID 0000-0001-9039-9067
Wei YueCollege of Pharmacy, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.ORCID 0000-0002-7444-2026
University at Buffalo, State University of New York · USUniversity of North Carolina at Chapel Hill · USAmgen (United States) · USAstraZeneca (United Kingdom) · GBJohnson & Johnson (United States) · USSimcyp (United Kingdom) · GBThe Ohio State University · USUniversity of Basel · CHUniversity of Helsinki · FIUniversity of Oklahoma Health Sciences Center · USUniversity of Rostock · DEUniversity of Toronto · CA

Funding

Mechanisms of Altered Hepatic Transport: Impact on Drug TherapyR35GM122576 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KIM L.R. BROUWER · 2017 to 2026
$5.7M
Prevention of paclitaxel-induced peripheral neuropathy with nilotinibR01CA238946 · NCI · OHIO STATE UNIVERSITY · PI HU, SHUIYING, LUSTBERG, MARYAM B. · 2019 to 2023
$2.9M
Regulation of hepatic uptake transporters by tyrosine kinasesR01GM139936 · NIGMS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI SPROWL, JASON A · 2021 to 2025
$2.3M
NCI NIH HHS R01 CA238946NIGMS NIH HHS R01 GM139936NIGMS NIH HHS R35 GM122576
6 · The paper itself

Abstract

Membrane transport proteins are involved in the absorption, disposition, efficacy, and/or toxicity of many drugs. Numerous mechanisms (e.g., nuclear receptors, epigenetic gene regulation, microRNAs, alternative splicing, post-translational modifications, and trafficking) regulate transport protein levels, localization, and function. Various factors associated with disease, medications, and dietary constituents, for example, may alter the regulation and activity of transport proteins in the intestine, liver, kidneys, brain, lungs, placenta, and other important sites, such as tumor tissue. This white paper reviews key mechanisms and regulatory factors that alter the function of clinically relevant transport proteins involved in drug disposition. Current considerations with in vitro and in vivo models that are used to investigate transporter regulation are discussed, including strengths, limitations, and the inherent challenges in predicting the impact of changes due to regulation of one transporter on compensatory pathways and overall drug disposition. In addition, translation and scaling of in vitro observations to in vivo outcomes are considered. The importance of incorporating altered transporter regulation in modeling and simulation approaches to predict the clinical impact on drug disposition is also discussed. Regulation of transporters is highly complex and, therefore, identification of knowledge gaps will aid in directing future research to expand our understanding of clinically relevant molecular mechanisms of transporter regulation. This information is critical to the development of tools and approaches to improve therapeutic outcomes by predicting more accurately the impact of regulation-mediated changes in transporter function on drug disposition and response.

Indexed as

Carrier ProteinsMembrane Transport ProteinsBiological TransportGene Expression RegulationHumansPharmaceutical PreparationsReceptors, Cytoplasmic and NuclearCarrier ProteinsMembrane Transport ProteinsPharmaceutical PreparationsReceptors, Cytoplasmic and Nuclear

Identifiers

PMID35390174
PMCPMC9398928
OpenAlexW4224235286

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.