Evidence map›Paper›PMID 36056771›Full record

ArticleClinical pharmacology and therapeutics2022

Physiologically-Based Pharmacokinetic Model Development, Validation, and Application for Prediction of Eliglustat Drug-Drug Interactions.

Siddhee A Sahasrabudhe, Shen Cheng, Mahmoud Al-Kofahi, Jeanine R Jarnes, Neal J Weinreb, Reena V Kartha

Open access · bronzeAbstract read
In one paragraph

Article in Clinical pharmacology and therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 22% 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
  6. 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

6 authors at 2 institutions in 1 country.

Siddhee A SahasrabudheCenter for Orphan Drug Research, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0002-8530-3427
Shen ChengDepartment of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0002-7493-4784
Mahmoud Al-KofahiDepartment of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0002-5458-0712
Jeanine R JarnesDepartment of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
Neal J WeinrebDepartment of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA.ORCID 0000-0001-9100-4733
Reena V KarthaCenter for Orphan Drug Research, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0002-1692-1539
University of Minnesota · USUniversity of Miami · US

Funding

Training & EducationU54NS065768 · NINDS · UNIVERSITY OF MINNESOTA · PI WHITLEY, CHESTER B. · 2009 to 2024
$17.7M
NINDS NIH HHS U54 NS065768
6 · The paper itself

Abstract

Eliglustat is a glucosylceramide synthase inhibitor indicated as a long-term substrate reduction therapy for adults with type 1 Gaucher disease, a lysosomal rare disease. It is primarily metabolized by cytochrome P450 2D6 (CYP2D6), and variants in the gene encoding this enzyme are important determinants of eliglustat pharmacokinetics (PK) and drug-drug interactions (DDIs). The existing drug label addresses the DDIs to some extent but has omitted scenarios where both metabolizing CYPs (2D6 and 3A4) are mildly or moderately inhibited. The objectives of this study were (i) to develop and validate an eliglustat physiologically-based pharmacokinetic (PBPK) model with and without drug interactions, (ii) to simulate untested DDI scenarios, and (iii) to explore potential dosing flexibility using lower dose strength of eliglustat (commercially not available). PK data from healthy adults receiving eliglustat with or without interacting drugs were obtained from literature and used for the PBPK model development and validation. The model-predicted single-dose and steady-state maximum concentration (C

Indexed as

Cytochrome P-450 CYP2D6KetoconazoleDrug InteractionsPyrrolidinesUnited StatesCytochrome P-450 CYP2D6eliglustatKetoconazolePyrrolidines

Identifiers

PMID36056771
PMCPMC9828395
OpenAlexW4294397886

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.