Evidence map›Paper›PMID 29520505›Full record

ArticlePharmaceutical research2018

Use of QSPR Modeling to Characterize In Vitro Binding of Drugs to a Gut-Restricted Polymer.

Christine Taylor Brew, James F Blake, Anita Mistry, Fengling Liu, Diana Carreno, Deidre Madsen, YongQi Mu, Martha Mayo, Wilhelm Stahl, David Matthews and 2 more

Open access · hybridAbstract readEvaluation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Pharmaceutical research, 2018. 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
0.3field-weighted citation impact, top 39% 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

1 citing paper in PubMed, 5 citations in OpenAlex.

  1. Review
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

12 authors at 2 institutions in 1 country.

Christine Taylor BrewResearch Department, Relypsa, Inc., a Vifor Pharma Group Company, 100 Cardinal Way, Redwood City, California, 94063, USA. tbrew@relypsa.com.
James F BlakeComputational Chemistry Department, Array BioPharma Inc, Boulder, Colorado, USA.
Anita MistryResearch Department, Relypsa, Inc., a Vifor Pharma Group Company, 100 Cardinal Way, Redwood City, California, 94063, USA.
Fengling LiuResearch Department, Relypsa, Inc., a Vifor Pharma Group Company, 100 Cardinal Way, Redwood City, California, 94063, USA.
Diana CarrenoResearch Department, Relypsa, Inc., a Vifor Pharma Group Company, 100 Cardinal Way, Redwood City, California, 94063, USA.
Deidre MadsenResearch Department, Relypsa, Inc., a Vifor Pharma Group Company, 100 Cardinal Way, Redwood City, California, 94063, USA.
YongQi MuResearch Department, Relypsa, Inc., a Vifor Pharma Group Company, 100 Cardinal Way, Redwood City, California, 94063, USA.
Martha MayoClinical Development, Relypsa, Inc., a Vifor Pharma Group Company, Redwood City, California, USA.
Wilhelm StahlTechnical Operations, Relypsa, Inc., a Vifor Pharma Group Company, Redwood City, California, USA.
David MatthewsResearch Department, Relypsa, Inc., a Vifor Pharma Group Company, 100 Cardinal Way, Redwood City, California, 94063, USA.
Derek MacleanResearch Department, Relypsa, Inc., a Vifor Pharma Group Company, 100 Cardinal Way, Redwood City, California, 94063, USA.
Steve HarrisonResearch Department, Relypsa, Inc., a Vifor Pharma Group Company, 100 Cardinal Way, Redwood City, California, 94063, USA.
Vifor Pharma (United States) · USArray BioPharma (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposePolymeric drugs, including patiromer (Veltassa®), bind target molecules or ions in the gut, allowing fecal elimination. Non-absorbed insoluble polymers, like patiromer, avoid common systemic drug-drug interactions (DDIs). However, the potential for DDI via polymer binding to orally administered drugs during transit of the gastrointestinal tract remains. Here we elucidate the properties correlated with drug-patiromer binding using quantitative structure-property relationship (QSPR) models.

methodsWe selected 28 drugs to evaluate for binding to patiromer in vitro over a range of pH and ionic conditions intended to mimic the gut environment. Using this in vitro data, we developed QSPR models using step-wise linear regression and analyzed over 100 physiochemical drug descriptors.

resultsFour descriptors emerged that account for ~70% of patiromer-drug binding in vitro: the computed surface area of hydrogen bond accepting atoms, ionization potential, electron affinity, and lipophilicity (R

conclusionsThese findings offer insight into drivers of in vitro binding to patiromer and describe a useful approach for assessing potential drug-binding risk of investigational polymeric drugs.

Indexed as

Models, BiologicalQuantitative Structure-Activity RelationshipAdministration, OralComputer SimulationDrug InteractionsGastrointestinal TransitHydrophobic and Hydrophilic InteractionsLinear ModelsMolecular StructurePharmaceutical ResearchPolymerspatiromerPolymersdrug interactionelectron affinityhydrogen bondingionization potentiallipophilicity

Identifiers

PMID29520505
PMCPMC5843698
OpenAlexW2790493728

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.