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

Tutkimustuotos: Lehtiartikkelivertaisarvioitu

Tutkijat

  • Marko Lamminsalo
  • Ella Taskinen
  • Timo Karvinen
  • Astrid Subrizi
  • Lasse Murtomäki

  • Arto Urtti
  • Veli Pekka Ranta

Organisaatiot

  • University of Eastern Finland
  • Comsol Oy
  • Aarhus University
  • University of Helsinki
  • St. Petersburg State University

Kuvaus

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.

Yksityiskohdat

AlkuperäiskieliEnglanti
Artikkeli153
JulkaisuPharmaceutical Research
Vuosikerta35
Numero8
TilaJulkaistu - 1 elokuuta 2018
OKM-julkaisutyyppiA1 Julkaistu artikkeli, soviteltu

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