Evidence map›Paper›PMID 33934558›Full record

ArticleCPT: pharmacometrics & systems pharmacology2021

Understanding effect site pharmacology of uprifosbuvir, a hepatitis C virus nucleoside inhibitor: Case study of a multidisciplinary modeling approach in drug development.

Paul van den Berg, Wei Gao, Maurice J Ahsman, Leticia Arrington, Filippos Kesisoglou, Randy Miller, Teun M Post, Matthew L Rizk

Open access · goldAbstract read
In one paragraph

Article in CPT: pharmacometrics & systems pharmacology, 2021. 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
0.1field-weighted citation impact, top 54% 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, 1 citations in OpenAlex.

  1. 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

8 authors at 2 institutions in 2 countries.

Paul van den BergLAP&P Consultants BV, Leiden, The Netherlands.
Wei GaoMerck & Co., Inc., Kenilworth, New Jersey, USA.
Maurice J AhsmanLAP&P Consultants BV, Leiden, The Netherlands.
Leticia ArringtonMerck & Co., Inc., Kenilworth, New Jersey, USA.
Filippos KesisoglouMerck & Co., Inc., Kenilworth, New Jersey, USA.
Randy MillerMerck & Co., Inc., Kenilworth, New Jersey, USA.
Teun M PostLAP&P Consultants BV, Leiden, The Netherlands.
Matthew L RizkMerck & Co., Inc., Kenilworth, New Jersey, USA.
Merck & Co., Inc., Rahway, NJ, USA (United States) · USPNO Consultants (Netherlands) · NL

Funding

Merck & Co., Inc.Merck Sharp & Dohme Corp.
6 · The paper itself

Abstract

Uprifosbuvir is a uridine nucleoside monophosphate prodrug inhibitor of the hepatitis C virus NS5B RNA polymerase. To quantitatively elucidate key metabolic pathways, assess the link between unmeasurable effect site concentrations and viral load reduction, and evaluate the influence of intrinsic and extrinsic factors on pharmacokinetics and pharmacodynamics, a model-informed drug development (MIDD) framework was initiated at an early stage. Originally scoped as a modeling effort focused on minimal physiologically based pharmacokinetic and covariate analyses, this project turned into a collaborative effort focused on gaining a deeper understanding of the data from drug metabolism, biopharmaceutics, pharmacometrics, and clinical pharmacology perspectives. This article presents an example of the practical execution of a MIDD-based, cooperative multidisciplinary modeling approach, creating a model that grows along with the team's integrated knowledge. Insights gained from this process could be used in forming optimal collaborations between disciplines in drug development for other investigative compounds.

Indexed as

Models, BiologicalAntiviral AgentsCooperative BehaviorDrug DevelopmentHepacivirusHepatitis CHumansRNA-Dependent RNA PolymeraseUridineViral LoadViral Nonstructural ProteinsAntiviral AgentsNS-5 protein, hepatitis C virusRNA-Dependent RNA PolymeraseuprifosbuvirUridineViral Nonstructural Proteins

Identifiers

PMID33934558
PMCPMC8302237
OpenAlexW3157183366

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.