Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Tools and Data Towards Supporting Quantitative Systems Pharmacology of the Eye – An Overview

Version 1 : Received: 9 March 2022 / Approved: 11 March 2022 / Online: 11 March 2022 (09:29:14 CET)

How to cite: Kuepfer, L.; Fuellen, G.; Stahnke, T. Tools and Data Towards Supporting Quantitative Systems Pharmacology of the Eye – An Overview. Preprints 2022, 2022030164 (doi: 10.20944/preprints202203.0164.v1). Kuepfer, L.; Fuellen, G.; Stahnke, T. Tools and Data Towards Supporting Quantitative Systems Pharmacology of the Eye – An Overview. Preprints 2022, 2022030164 (doi: 10.20944/preprints202203.0164.v1).

Abstract

Good eyesight belongs to the most-valued attributes of health, and diseases of the eye are a significant health care burden. Case numbers are expected to further increase in the next decades due to an aging society. The development of drugs in ophthalmology, however, is difficult due to limited accessibility of the eye, in terms of drug administration and in terms of sampling of tissues for drug pharmacokinetics (PK) and pharmacodynamics (PD). Ocular quantitative systems pharmacology (QSP) models provide the opportunity to describe the distribution of drugs in the eye as well as the resulting drug-response in specific segments of the eye. In particular, ocular physiologically-based pharmacokinetic (PBPK) models are necessary to describe drug concentration levels in different regions of the eye. Further, ocular effect models employing molecular data from specific cellular systems are needed to develop dose-response correlations. We here describe the current status of PK/PBPK as well as PD models for the eye and describe cellular systems, data repositories as well as animal models in ophthalmology. The application of the various concepts is highlighted for the development of new treatments for post-operative fibrosis after glaucoma surgery.

Keywords

QSP; PBPK; glaucoma; primary human tenon fibroblasts; josamycin; connectivity map

Subject

MEDICINE & PHARMACOLOGY, Ophthalmology

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