Evidence map›Paper›PMID 41136823›Full record

ArticleThe AAPS journal2025

Mechanistic Modeling of Intramuscular Administration of a Long-acting Injectable Accounting for Tissue Response At the Depot Site.

Daniela A Silva, Maxime Le Merdy, James Mullin, Nilesh Malavia, Khondoker Alam, Eleftheria Tsakalozou, Abdullah Al Shoyaib, Yan Wang, Diane Burgess, Viera Lukacova

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The AAPS journal, 2025. 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
–field-weighted citation impact
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. 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

10 authors.

Daniela A SilvaSimulations Plus, Inc., Research Triangle Park, PO Box 12317, Durham, NC, 27709, USA. daniela.silva@simulations-plus.com.ORCID 0000-0003-1073-5548
Maxime Le MerdySimulations Plus, Inc., Research Triangle Park, PO Box 12317, Durham, NC, 27709, USA.ORCID 0000-0003-2629-8039
James MullinSimulations Plus, Inc., Research Triangle Park, PO Box 12317, Durham, NC, 27709, USA.ORCID 0009-0008-8262-7355
Nilesh MalaviaDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USA.ORCID 0009-0008-6728-7268
Khondoker AlamOffice of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.ORCID 0000-0001-8757-2412
Eleftheria TsakalozouOffice of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.ORCID 0000-0003-1993-8528
Abdullah Al ShoyaibOffice of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.ORCID 0000-0001-6168-1645
Yan WangOffice of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.ORCID 0009-0005-8643-2908
Diane BurgessDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USA.
Viera LukacovaSimulations Plus, Inc., Research Triangle Park, PO Box 12317, Durham, NC, 27709, USA.ORCID 0009-0004-4197-4570

Funding

FDA HHS U01 FD008304
6 · The paper itself

Abstract

The tissue response to long-acting injectables (LAIs) suspension injection may impact the product in vivo performance. One such response is the formation of an inflammatory cell layer (ICL) resulting in an envelope around the injected particles. This study aims to use a mechanistic model to describe the clinical in vivo exposure and performance of an intramuscular LAI suspension and evaluate impact of ICL physiological response at the injection site in humans. Aripiprazole lauroxil (AR-L) was used as the model drug. A baseline pharmacokinetics model was built and validated for aripiprazole. The impact of inflammation on the LAI in vivo performance was assessed by including an ICL model. The developed pharmacokinetic model adequately described the observed plasma profiles of AR following intravenous and oral administration in humans. The initial intramuscular predictions assumed that the absorption rate is dependent on the dissolution and partitioning of AR-L into the systemic circulation from the intramuscular (IM) depot. The simulation resulted in a shape mismatch between the simulated and observed data and an earlier predicted T

Indexed as

Antipsychotic AgentsAripiprazoleModels, BiologicalAdministration, OralComputer SimulationDelayed-Action PreparationsHumansInflammationInjections, IntramuscularMaleSuspensionsAntipsychotic AgentsAripiprazoleDelayed-Action PreparationsSuspensionsimmune responseintramuscular depotlong-acting injectables

Identifiers

PMID41136823
PMCPMC12591097

What OpenQuestion holds

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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.