Evidence map›Paper›PMID 31451949›Full record

ArticlePharmaceutical research2019

Assessing the Utility of In Vitro Screening Tools for Predicting Bio-Performance of Oral Peptide Delivery.

Prajakta Gadgil, Candice Alleyne, Kung-I Feng, Mengwei Hu, Marian Gindy, Alexei V Buevich, Scott Fauty, Gino Salituro, Jianzhong Wen, Ying Li and 3 more

Abstract read
PubMed Publisher
In one paragraph

Article in Pharmaceutical research, 2019. 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
1.3field-weighted citation impact, top 24% 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, 19 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

13 authors at 1 institution in 1 country.

Prajakta GadgilDepartment of Discovery Pharmaceutical Sciences, Merck & Co., Inc., 126 East Lincoln Ave, Rahway, New Jersey, 07065, USA. pgadgil87@gmail.com.
Candice AlleyneDepartment of Discovery Pharmaceutical Sciences, Merck & Co., Inc., 126 East Lincoln Ave, Rahway, New Jersey, 07065, USA.
Kung-I FengDepartment of Discovery Pharmaceutical Sciences, Merck & Co., Inc., 126 East Lincoln Ave, Rahway, New Jersey, 07065, USA.
Mengwei HuDepartment of Discovery Pharmaceutical Sciences, Merck & Co., Inc., 126 East Lincoln Ave, Rahway, New Jersey, 07065, USA.
Marian GindyDepartment of Discovery Pharmaceutical Sciences, Merck & Co., Inc., 126 East Lincoln Ave, Rahway, New Jersey, 07065, USA.
Alexei V BuevichDepartment of NMR Structure Elucidation, Merck & Co., Inc., Kenilworth, New Jersey, USA.
Scott FautyDepartment of Safety Assessment and Laboratory Animal Resources, Merck & Co., Inc., Kenilworth, New Jersey, USA.
Gino SalituroDepartment of Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Inc., Kenilworth, New Jersey, USA.
Jianzhong WenDepartment of Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Inc., Kenilworth, New Jersey, USA.
Ying LiDepartment of Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Inc., Kenilworth, New Jersey, USA.
Rebecca NofsingerDepartment of Biopharmaceutics and Specialty Dosage Form, Merck & Co., Inc., Kenilworth, New Jersey, USA.
Tomi K SawyerDepartment of Discovery Chemistry Modalities, Merck & Co., Inc., Kenilworth, New Jersey, USA.
Nicole BuistDepartment of Discovery Pharmaceutical Sciences, Merck & Co., Inc., 126 East Lincoln Ave, Rahway, New Jersey, 07065, USA.
Merck & Co., Inc., Rahway, NJ, USA (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeIn this study we evaluated the utility of in-vitro screening tools for predicting the in-vivo behavior of six cyclic peptides with different solubility and permeability properties (BCS class II and III), intended for oral delivery in presence of permeation enhancer Labrasol.

methodsAn in vitro flux assay was used to assess peptide permeation across a biomimetic, lipid-based membrane and in vivo studies in rats were used to determine oral peptide bioavailability in the presence of Labrasol.

resultsThe in vitro flux was significantly increased for BCS class III peptides, while it significantly decreased or remained unchanged for BCS class II peptides with increasing Labrasol concentrations. The different flux responses were attributed to the combination of reduced effective free peptide concentration and increased membrane permeability in the presence of Labrasol. In vivo studies in male Wistar-Hans rats indicated improved oral bioavailability at different extents for all peptides in presence of Labrasol. On comparing the in vitro and in vivo data, a potential direct correlation for BCS class III peptides was seen but not for BCS class II peptides, due to lower free concentrations of peptides in this class.

conclusionThis study assessed the utility of in vitro screening tools for selecting peptides and permeation excipients early in drug product development. Graphical Abstract Graphical Abstract and Figure 1 contains small text.Graphical Abstract text is made larger. The Figure 1 text cannot be made larger.

Indexed as

Administration, OralAnimalsBiological AvailabilityCell Membrane PermeabilityChemistry, PharmaceuticalExcipientsGlyceridesLipid BilayersMaleModels, BiologicalPeptides, CyclicRats, WistarSolubilityExcipientsGlyceridesLabrasolLipid BilayersPeptides, Cyclicfluxoral deliverypeptidespermeation enhancer

Identifiers

PMID31451949
OpenAlexW2970404052

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.