Extended Pharmacokinetic Model of the Rabbit Eye for Intravitreal and Intracameral Injections of Macromolecules: Quantitative Analysis of Anterior and Posterior Elimination Pathways

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Extended Pharmacokinetic Model of the Rabbit Eye for Intravitreal and Intracameral Injections of Macromolecules : Quantitative Analysis of Anterior and Posterior Elimination Pathways. / Lamminsalo, Marko; Taskinen, Ella; Karvinen, Timo; Subrizi, Astrid; Murtomäki, Lasse; Urtti, Arto; Ranta, Veli Pekka.

In: Pharmaceutical Research, Vol. 35, No. 8, 153, 01.08.2018.

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@article{5512d224ac1d413f81d365b0309244b0,
title = "Extended Pharmacokinetic Model of the Rabbit Eye for Intravitreal and Intracameral Injections of Macromolecules: Quantitative Analysis of Anterior and Posterior Elimination Pathways",
abstract = "Purpose: To extend the physiological features of the anatomically accurate model of the rabbit eye for intravitreal (IVT) and intracameral (IC) injections of macromolecules. Methods: The computational fluid dynamic model of the rabbit eye by Missel (2012) was extended by enhancing the mixing in the anterior chamber with thermal gradient, heat transfer and gravity, and studying its effect on IC injections of hyaluronic acids. In IVT injections of FITC-dextrans (MW 10–157 kDa) the diffusion though retina was defined based on published in vitro data. Systematic changes in retinal permeability and convective transport were made, and the percentages of anterior and posterior elimination pathways were quantified. Simulations were compared with published in vivo data. Results: With the enhanced mixing the elimination half-lives of hyaluronic acids after IC injection were 62–100 min that are similar to in vivo data and close to the theoretical value for the well-stirred anterior chamber (57 min). In IVT injections of FITC-dextrans a good match between simulations and in vivo data was obtained when the percentage of anterior elimination pathway was over 80{\%}. Conclusions: The simulations with the extended model closely resemble in vivo pharmacokinetics, and the model is a valuable tool for data interpretation and predictions.",
keywords = "computational fluid dynamics, intracameral injection, intravitreal injection, macromolecule, ocular pharmacokinetics",
author = "Marko Lamminsalo and Ella Taskinen and Timo Karvinen and Astrid Subrizi and Lasse Murtom{\"a}ki and Arto Urtti and Ranta, {Veli Pekka}",
year = "2018",
month = "8",
day = "1",
doi = "10.1007/s11095-018-2435-0",
language = "English",
volume = "35",
journal = "Pharmaceutical Research",
issn = "0724-8741",
number = "8",

}

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TY - JOUR

T1 - Extended Pharmacokinetic Model of the Rabbit Eye for Intravitreal and Intracameral Injections of Macromolecules

T2 - Quantitative Analysis of Anterior and Posterior Elimination Pathways

AU - Lamminsalo, Marko

AU - Taskinen, Ella

AU - Karvinen, Timo

AU - Subrizi, Astrid

AU - Murtomäki, Lasse

AU - Urtti, Arto

AU - Ranta, Veli Pekka

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Purpose: To extend the physiological features of the anatomically accurate model of the rabbit eye for intravitreal (IVT) and intracameral (IC) injections of macromolecules. Methods: The computational fluid dynamic model of the rabbit eye by Missel (2012) was extended by enhancing the mixing in the anterior chamber with thermal gradient, heat transfer and gravity, and studying its effect on IC injections of hyaluronic acids. In IVT injections of FITC-dextrans (MW 10–157 kDa) the diffusion though retina was defined based on published in vitro data. Systematic changes in retinal permeability and convective transport were made, and the percentages of anterior and posterior elimination pathways were quantified. Simulations were compared with published in vivo data. Results: With the enhanced mixing the elimination half-lives of hyaluronic acids after IC injection were 62–100 min that are similar to in vivo data and close to the theoretical value for the well-stirred anterior chamber (57 min). In IVT injections of FITC-dextrans a good match between simulations and in vivo data was obtained when the percentage of anterior elimination pathway was over 80%. Conclusions: The simulations with the extended model closely resemble in vivo pharmacokinetics, and the model is a valuable tool for data interpretation and predictions.

AB - Purpose: To extend the physiological features of the anatomically accurate model of the rabbit eye for intravitreal (IVT) and intracameral (IC) injections of macromolecules. Methods: The computational fluid dynamic model of the rabbit eye by Missel (2012) was extended by enhancing the mixing in the anterior chamber with thermal gradient, heat transfer and gravity, and studying its effect on IC injections of hyaluronic acids. In IVT injections of FITC-dextrans (MW 10–157 kDa) the diffusion though retina was defined based on published in vitro data. Systematic changes in retinal permeability and convective transport were made, and the percentages of anterior and posterior elimination pathways were quantified. Simulations were compared with published in vivo data. Results: With the enhanced mixing the elimination half-lives of hyaluronic acids after IC injection were 62–100 min that are similar to in vivo data and close to the theoretical value for the well-stirred anterior chamber (57 min). In IVT injections of FITC-dextrans a good match between simulations and in vivo data was obtained when the percentage of anterior elimination pathway was over 80%. Conclusions: The simulations with the extended model closely resemble in vivo pharmacokinetics, and the model is a valuable tool for data interpretation and predictions.

KW - computational fluid dynamics

KW - intracameral injection

KW - intravitreal injection

KW - macromolecule

KW - ocular pharmacokinetics

UR - http://www.scopus.com/inward/record.url?scp=85048019880&partnerID=8YFLogxK

U2 - 10.1007/s11095-018-2435-0

DO - 10.1007/s11095-018-2435-0

M3 - Article

VL - 35

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 8

M1 - 153

ER -

ID: 25728727