Pharmacokinetic Simulations of Intravitreal Biologicals

Aspects of Drug Delivery to the Posterior and Anterior Segments

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Biologicals are important ocular drugs that are be delivered using monthly and bimonthly intravitreal injections to treat retinal diseases, such as age-related macular degeneration. Long acting delivery systems are needed for prolongation of their dosing interval. Intravitreal biologicals are eliminated from the eye via the aqueous humor outflow. Thus, the anterior and posterior segments are exposed to the drug. We utilized a kinetic simulation model to estimate protein drug concentrations in the vitreous and aqueous humor after bolus injection and controlled release administration to the vitreous. The simulations predicted accurately the experimental levels of 5 biologicals in the vitreous and aqueous humor. The good match between the simulations and experimental data demonstrated almost complete anterior segment bioavailability, and major dose sparing with ocular controlled release systems. Overall, the model is a useful tool in the design of intraocular delivery of biologicals.
Original languageEnglish
Article number9
JournalPharmaceutics
Volume11
Issue number1
Number of pages11
ISSN1999-4923
DOIs
Publication statusPublished - 30 Dec 2018
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 317 Pharmacy
  • intravitreal inject ion
  • ocular drug delivery
  • bevacizumab
  • ranibizumab
  • aflibercept
  • controlled release
  • RABBIT
  • VOLUME
  • CLEARANCE
  • RITUXIMAB
  • THERAPY
  • PROTEIN

Cite this

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title = "Pharmacokinetic Simulations of Intravitreal Biologicals: Aspects of Drug Delivery to the Posterior and Anterior Segments",
abstract = "Biologicals are important ocular drugs that are be delivered using monthly and bimonthly intravitreal injections to treat retinal diseases, such as age-related macular degeneration. Long acting delivery systems are needed for prolongation of their dosing interval. Intravitreal biologicals are eliminated from the eye via the aqueous humor outflow. Thus, the anterior and posterior segments are exposed to the drug. We utilized a kinetic simulation model to estimate protein drug concentrations in the vitreous and aqueous humor after bolus injection and controlled release administration to the vitreous. The simulations predicted accurately the experimental levels of 5 biologicals in the vitreous and aqueous humor. The good match between the simulations and experimental data demonstrated almost complete anterior segment bioavailability, and major dose sparing with ocular controlled release systems. Overall, the model is a useful tool in the design of intraocular delivery of biologicals.",
keywords = "317 Pharmacy, intravitreal inject ion, ocular drug delivery, bevacizumab, ranibizumab, aflibercept, controlled release, RABBIT, VOLUME, CLEARANCE, RITUXIMAB, THERAPY, PROTEIN",
author = "Anna-Kaisa Rimpel{\"a} and Iiro Kiiski and Feng Deng and Heidi Kidron and Arto Urtti",
year = "2018",
month = "12",
day = "30",
doi = "10.3390/pharmaceutics11010009",
language = "English",
volume = "11",
journal = "Pharmaceutics",
issn = "1999-4923",
publisher = "MDPI",
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TY - JOUR

T1 - Pharmacokinetic Simulations of Intravitreal Biologicals

T2 - Aspects of Drug Delivery to the Posterior and Anterior Segments

AU - Rimpelä, Anna-Kaisa

AU - Kiiski, Iiro

AU - Deng, Feng

AU - Kidron, Heidi

AU - Urtti, Arto

PY - 2018/12/30

Y1 - 2018/12/30

N2 - Biologicals are important ocular drugs that are be delivered using monthly and bimonthly intravitreal injections to treat retinal diseases, such as age-related macular degeneration. Long acting delivery systems are needed for prolongation of their dosing interval. Intravitreal biologicals are eliminated from the eye via the aqueous humor outflow. Thus, the anterior and posterior segments are exposed to the drug. We utilized a kinetic simulation model to estimate protein drug concentrations in the vitreous and aqueous humor after bolus injection and controlled release administration to the vitreous. The simulations predicted accurately the experimental levels of 5 biologicals in the vitreous and aqueous humor. The good match between the simulations and experimental data demonstrated almost complete anterior segment bioavailability, and major dose sparing with ocular controlled release systems. Overall, the model is a useful tool in the design of intraocular delivery of biologicals.

AB - Biologicals are important ocular drugs that are be delivered using monthly and bimonthly intravitreal injections to treat retinal diseases, such as age-related macular degeneration. Long acting delivery systems are needed for prolongation of their dosing interval. Intravitreal biologicals are eliminated from the eye via the aqueous humor outflow. Thus, the anterior and posterior segments are exposed to the drug. We utilized a kinetic simulation model to estimate protein drug concentrations in the vitreous and aqueous humor after bolus injection and controlled release administration to the vitreous. The simulations predicted accurately the experimental levels of 5 biologicals in the vitreous and aqueous humor. The good match between the simulations and experimental data demonstrated almost complete anterior segment bioavailability, and major dose sparing with ocular controlled release systems. Overall, the model is a useful tool in the design of intraocular delivery of biologicals.

KW - 317 Pharmacy

KW - intravitreal inject ion

KW - ocular drug delivery

KW - bevacizumab

KW - ranibizumab

KW - aflibercept

KW - controlled release

KW - RABBIT

KW - VOLUME

KW - CLEARANCE

KW - RITUXIMAB

KW - THERAPY

KW - PROTEIN

U2 - 10.3390/pharmaceutics11010009

DO - 10.3390/pharmaceutics11010009

M3 - Article

VL - 11

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 1

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ER -