Evidence map›Paper›PMID 34458976›Full record

ArticleClinical pharmacokinetics2022

Physiologically Based Pharmacokinetic Modelling of Inhaled Nemiralisib: Mechanistic Components for Pulmonary Absorption, Systemic Distribution, and Oral Absorption.

Neil A Miller, Rebecca H Graves, Chris D Edwards, Augustin Amour, Ed Taylor, Olivia Robb, Brett O'Brien, Aarti Patel, Andrew W Harrell, Edith M Hessel

Open access · hybridAbstract read
In one paragraph

Article in Clinical pharmacokinetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.6field-weighted citation impact, top 15% 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

8 citing papers in PubMed, 14 citations in OpenAlex.

  1. Trial
  2. Best Practices in Physiologically Based Pharmacokinetic (PBPK) Modeling.CPT: pharmacometrics & systems pharmacology · 2026
    Review
  3. A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026
    Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. 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

10 authors at 3 institutions in 3 countries.

Neil A MillerSimulations Plus, Inc., 42505 10th Street West, Lancaster, CA, 93534, USA. neil@simulations-plus.com.ORCID 0000-0003-3077-5790
Rebecca H GravesSimulations Plus, Inc., 42505 10th Street West, Lancaster, CA, 93534, USA.
Chris D EdwardsGlaxoSmithKline R&D, Stevenage, Hertfordshire, UK.
Augustin AmourGlaxoSmithKline R&D, Stevenage, Hertfordshire, UK.
Ed TaylorGlaxoSmithKline R&D, Gunnelswood Road, Ware, Hertfordshire, UK.
Olivia RobbGlaxoSmithKline R&D, Stevenage, Hertfordshire, UK.
Brett O'BrienGlaxoSmithKline R&D, Stevenage, Hertfordshire, UK.
Aarti PatelGlaxoSmithKline R&D, Gunnelswood Road, Ware, Hertfordshire, UK.
Andrew W HarrellGlaxoSmithKline R&D, Gunnelswood Road, Ware, Hertfordshire, UK.
Edith M HesselEligo Bioscience, Paris, France.
GlaxoSmithKline (United Kingdom) · GBSimulations Plus (United States) · USEligo Bioscience (France) · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesPhysiologically based pharmacokinetic (PBPK) modelling has evolved to accommodate different routes of drug administration and enables prediction of drug concentrations in tissues as well as plasma. The inhalation route of administration has proven successful in treating respiratory diseases but can also be used for rapid systemic delivery, holding great promise for treatment of diseases requiring systemic exposure. The objective of this work was to develop a PBPK model that predicts plasma and tissue concentrations following inhalation administration of the PI3Kδ inhibitor nemiralisib.

methodsA PBPK model was built in GastroPlus

resultsThe inhaled PBPK model was verified using plasma and bronchoalveolar lavage fluid concentration data obtained in human subjects. Prediction of tissue concentrations using the permeability-limited systemic disposition tissue model was further validated using tissue concentration data obtained in the rat following intravenous infusion administration to steady state.

conclusionsFully mechanistic inhaled PBPK models such as the model described herein could be applied for cross molecule assessments with respect to lung retention and systemic exposure, both in terms of pharmacology and toxicology, and may facilitate clinical indication selection.

Indexed as

IndazolesModels, BiologicalAbsorption, PhysiologicalAdministration, InhalationAdministration, OralAnimalsComputer SimulationHumansIndolesOxazolesPiperazinesRatsIndazolesIndolesNemiralisibOxazolesPiperazines

Identifiers

PMID34458976
PMCPMC8813803
OpenAlexW3197452721

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.