Evidence map›Paper›PMID 36959411›Full record

ArticlePharmaceutical research2023

Computational Model of In Vivo Corneal Pharmacokinetics and Pharmacodynamics of Topically Administered Ophthalmic Drug Products.

Carrie German, Zhijian Chen, Andrzej Przekwas, Ross Walenga, Andrew Babiskin, Liang Zhao, Jianghong Fan, Ming-Liang Tan

Abstract read
PubMed Publisher
In one paragraph

Article in Pharmaceutical research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

3 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Article
  3. Mathematical Models of Ocular Drug Delivery.Investigative ophthalmology & visual science · 2024
    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

8 authors at 2 institutions in 1 country.

Carrie GermanCFD Research Corporation, Computational Biology Division, 6820 Moquin Dr NW, Huntsville, AL, 35806, USA. carrie.german@cfd-research.com.ORCID http://orcid.org/0000-0003-0550-3603
Zhijian ChenCFD Research Corporation, Computational Biology Division, 6820 Moquin Dr NW, Huntsville, AL, 35806, USA.
Andrzej PrzekwasCFD Research Corporation, Computational Biology Division, 6820 Moquin Dr NW, Huntsville, AL, 35806, USA.
Ross WalengaDivision of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.
Andrew BabiskinDivision of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.
Liang ZhaoDivision of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.
Jianghong FanDivision of Pharmacometrics, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.
Ming-Liang TanDivision of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.
United States Food and Drug Administration · USCFD Research Corporation (United States) · US

Funding

Computational Biology (Cobi) Tools as a Framework for Physiologically-Based Pharmacokinetic/Pharmacodynamic Model Extrapolation from Rabbit to Human for Ophthalmic Drug ProductsU01FD006929 · FDA · CFD RESEARCH CORPORATION · PI GERMAN, CARRIE · 2020 to 2022
$400k
FDA HHS U01 FD006929
6 · The paper itself

Abstract

introductionAlthough the eye is directly accessible on the surface of the human body, drug delivery can be extremely challenging due to the presence of multiple protective barriers in eye tissues. Researchers have developed complex formulation strategies to overcome these barriers to ophthalmic drug delivery. Current development strategies rely heavily on in vitro experiments and animal testing to predict human pharmacokinetics (PK) and pharmacodynamics (PD).

objectiveThe primary objective of the study was to develop a high-fidelity PK/PD model of the anterior eye for topical application of ophthalmic drug products.

methodsHere, we present a physiologically-based in silico approach to predicting PK and PD in rabbits after topical administration of ophthalmic products. A first-principles based approach was used to describe timolol dissolution, transport, and distribution, including consideration of ionized transport, following topical instillation of a timolol suspension.

resultsUsing literature transport and response parameters, the computational model described well the concentration-time and response-time profiles in rabbit. Comparison of validated rabbit model results and extrapolated human model results demonstrate observable differences in the distribution of timolol at multiple time points.

conclusionThis modeling framework provides a tool for model-based prediction of PK in eye tissues and PD after topical ophthalmic drug administration to the eyes.

Indexed as

EyeTimololAdministration, TopicalAnimalsCorneaHumansOphthalmic SolutionsRabbitsOphthalmic SolutionsTimololcomputational modelingocularPBPKpharmacodynamicstimolol

Identifiers

PMID36959411
OpenAlexW4360609271

What OpenQuestion holds

Textmetadata
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.