Evidence map›Paper›PMID 32142598›Full record

ArticleCPT: pharmacometrics & systems pharmacology2020

Prediction of Clinical Transporter-Mediated Drug-Drug Interactions via Comeasurement of Pitavastatin and Eltrombopag in Human Hepatocyte Models.

Simon J Carter, Bhavik Chouhan, Pradeep Sharma, Michael J Chappell

Open access · goldAbstract readValidation Study
In one paragraph

Article in CPT: pharmacometrics & systems pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.1field-weighted citation impact, top 58% 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

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

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

4 authors at 3 institutions in 2 countries.

Simon J CarterBiomedical and Biological Systems Laboratory, School of Engineering, University of Warwick, Coventry, UK.
Bhavik ChouhanFunctional & Mechanistic Safety, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca R&D, Gothenburg, Sweden.
Pradeep SharmaClinical Pharmacology & Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca R&D, Cambridge, UK.
Michael J ChappellBiomedical and Biological Systems Laboratory, School of Engineering, University of Warwick, Coventry, UK.
University of Warwick · GBAstraZeneca (Sweden) · SEAstraZeneca (United Kingdom) · GB

Funding

Biotechnology and Biological Sciences Research Council 1548253
6 · The paper itself

Abstract

A structurally identifiable micro-rate constant mechanistic model was used to describe the interaction between pitavastatin and eltrombopag, with improved goodness-of-fit values through comeasurement of pitavastatin and eltrombopag. Transporter association and dissociation rate constants and passive rates out of the cell were similar between pitavastatin and eltrombopag. Translocation into the cell through transporter-mediated uptake was six times greater for pitavastatin, leading to pronounced inhibition of pitavastatin uptake by eltrombopag. The passive rate into the cell was 91 times smaller for pitavastatin compared with eltrombopag. A semimechanistic physiologically-based pharmacokinetic (PBPK) model was developed to evaluate the potential for clinical drug-drug interactions (DDIs). The PBPK model predicted a twofold increase in the pitavastatin peak blood concentration and area under the concentration-time curve in the presence of eltrombopag in simulated healthy volunteers. The use of structural identifiability supporting experimental design combined with robust micro-rate constant parameter estimates and a semimechanistic PBPK model gave more informed predictions of transporter-mediated DDIs.

Indexed as

Models, BiologicalAdultArea Under CurveBenzoatesBiological TransportDrug InteractionsHepatocytesHumansHydrazinesHydroxymethylglutaryl-CoA Reductase InhibitorsMembrane Transport ProteinsPyrazolesQuinolinesBenzoateseltrombopagHydrazinesHydroxymethylglutaryl-CoA Reductase InhibitorsMembrane Transport ProteinspitavastatinPyrazolesQuinolines

Identifiers

PMID32142598
PMCPMC7179958
OpenAlexW3009092112

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.