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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  • Marko Lamminsalo, University of Eastern Finland
  • ,
  • Ella Taskinen, University of Eastern Finland
  • ,
  • Timo Karvinen, Comsol Oy
  • ,
  • Astrid Subrizi
  • ,
  • Lasse Murtomäki, Aalto University
  • ,
  • Arto Urtti, University of Eastern Finland, Helsingin yliopisto, Saint Petersburg State University
  • ,
  • Veli Pekka Ranta, University of Eastern Finland

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.

Original languageEnglish
Article number153
JournalPharmaceutical Research
Volume35
Issue8
ISSN0724-8741
DOIs
Publication statusPublished - 1 Aug 2018

    Research areas

  • computational fluid dynamics, intracameral injection, intravitreal injection, macromolecule, ocular pharmacokinetics

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