Evidence map›Paper›PMID 30825461›Full record

ArticleJournal of pharmaceutical sciences2019

Increased Expression of Renal Drug Transporters in a Mouse Model of Familial Alzheimer's Disease.

Yijun Pan, Kotaro Omori, Izna Ali, Masanori Tachikawa, Tetsuya Terasaki, Kim L R Brouwer, Joseph A Nicolazzo

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of pharmaceutical sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.0field-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

7 citing papers in PubMed, 14 citations in OpenAlex.

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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

7 authors at 3 institutions in 3 countries.

Yijun PanDrug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 399 Royal Parade, Parkville, Victoria 3052, Australia.
Kotaro OmoriDivision of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
Izna AliUNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 301 Pharmacy Lane, Chapel Hill, North Carolina 27599.
Masanori TachikawaDivision of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
Tetsuya TerasakiDivision of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
Kim L R BrouwerUNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 301 Pharmacy Lane, Chapel Hill, North Carolina 27599.
Joseph A NicolazzoDrug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 399 Royal Parade, Parkville, Victoria 3052, Australia. Electronic address: Joseph.Nicolazzo@monash.edu.
Tohoku University · JPMonash University · AUUniversity of North Carolina at Chapel Hill · US

Funding

UNC-Duke Collaborative Clinical Pharmacology Postdoctoral Training Program-Evaluation SupplementT32GM086330 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KIM L.R. BROUWER, Daniel Gonzalez · 2011 to 2026
$8.5M
ALTERED HEPATIC DISPOSITION OF ANIONIC DRUGS-MECHANISMSR01GM041935 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BROUWER, KIM L.R. · 1997 to 2016
$6.5M
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
NIGMS NIH HHS R01 GM041935NIGMS NIH HHS R35 GM122576NIGMS NIH HHS T32 GM086330
6 · The paper itself

Abstract

It is well established that the expression and function of drug transporters at the blood-brain barrier are altered in Alzheimer's disease (AD). However, we recently demonstrated in a mouse model of AD that the expression of key drug transporters and metabolizing enzymes was modified in peripheral organs, such as the small intestine and liver, suggesting that systemic drug absorption may be altered in AD. The purpose of this study was to determine whether the expression of drug transporters in the kidneys differed between 8- to 9-month-old wild-type mice and APPswe/PSEN1dE9 (APP/PS1) transgenic mice, a mouse model of familial AD, using a quantitative targeted absolute proteomics approach. The protein expression of the drug transporters-multidrug resistance-associated protein 2, organic anion transporter 3, and organic cation transporter 2-was upregulated 1.6-, 1.3-, and 1.4-fold, respectively, in kidneys from APP/PS1 mice relative to wild-type mice. These results suggest that in addition to modified oral absorption of certain drugs, it is possible that the renal excretion of drugs that are multidrug resistance-associated protein 2, organic anion transporter 3, and organic cation transporter 2 substrates could be altered in AD. These changes could affect the interpretation of studies conducted during drug development using this mouse model of AD and potentially impact dosage regimens of such drugs prescribed in this patient population.

Indexed as

Alzheimer DiseaseAnimalsATP-Binding Cassette, Sub-Family C ProteinsBiological TransportBlood-Brain BarrierDisease Models, AnimalFemaleKidneyLiverMembrane Transport ProteinsMice, TransgenicMultidrug Resistance-Associated Protein 2Organic Anion TransportersATP-Binding Cassette, Sub-Family C ProteinsMembrane Transport ProteinsMultidrug Resistance-Associated Protein 2Organic Anion TransportersAlzheimer's diseasemultidrug resistance-associated protein(s) (MDR)organic anion transporter(s) (OAT)organic cation transporter(s) (OCT)renal transporttransporters

Identifiers

PMID30825461
PMCPMC6888996
OpenAlexW2918167924

What OpenQuestion holds

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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.