Evidence map›Paper›PMID 36635486›Full record

ArticlePharmaceutical research2023

Prediction of the Renal Organic Anion Transporter 1 (OAT1)- Mediated Drug Interactions for LY404039, the Active Metabolite of Pomaglumetad Methionil.

Y Anne Pak, Maria M Posada, James Bacon, Amanda Long, William Annes, Jennifer Witcher, Malcolm Mitchell, Rommel G Tirona, Stephen D Hall, Kathleen M Hillgren

Abstract read
PubMed Publisher
In one paragraph

Article in Pharmaceutical research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.4field-weighted citation impact, top 17% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Article
  3. 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

10 authors at 2 institutions in 2 countries.

Y Anne PakEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
Maria M PosadaEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. mmposada@lilly.com.
James BaconEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
Amanda Long
William AnnesEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
Jennifer WitcherEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
Malcolm MitchellEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
Rommel G TironaDivision of Clinical Pharmacology, Department of Medicine, The University of Western Ontario, London, ON, Canada.
Stephen D HallEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
Kathleen M HillgrenEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
Eli Lilly (United States) · USWestern University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeThe objective of this work was to demonstrate that clinical OAT1-mediated DDIs can be predicted using physiologically based pharmacokinetic (PBPK) modeling.

methodsLY404039 is a metabotropic glutamate receptor 2/3 agonist and the active moiety of the prodrug pomaglumetad methionil (LY2140023). After oral administration, pomaglumetad methionil is rapidly taken up by enterocytes via PEPT1 and once absorbed, converted to LY404039 via membrane dehydropeptidase 1 (DPEP1). LY404039 is renally excreted by both glomerular filtration and active secretion and in vitro studies showed that the active secretion of LY404039 was mediated by the organic anion transporter 1 (OAT1). Both clinical and in vitro data were used to build a PBPK model to predict OAT1-mediated DDIs.

resultsIn vitro inhibitory potencies (IC

conclusionsOAT1- mediated DDIs can be predicted using in vitro measured IC

Indexed as

Amino AcidsBridged Bicyclo Compounds, HeterocyclicCyclic S-OxidesDrug InteractionsAdultFemaleHumansMaleMiddle AgedModels, BiologicalOrganic Anion Transport Protein 1Prodrugs4-aminho-2-thiabicyclo(3.1.0)hexane-4,6-dicarboxylic acidAmino AcidsBridged Bicyclo Compounds, HeterocyclicCyclic S-OxidesLY 2140023Organic Anion Transport Protein 1ProdrugsSLC22A6 protein, humanactive transportdrug interactionorganic anion transportersPBPK modelrenal transporters

Identifiers

PMID36635486
OpenAlexW4315778133

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.