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Models and approaches describing metabolism, transport, and toxicity of drugs administered by the ocular route

Dumouchel, Jennifer and Chemuturi, Nagendra and Milton, Mark and Camenisch, Gian P. and Chastain, Jim and Walles, Markus and Sasseville, Vito and Gunduz, Mithat and Iyer, Ganesh and Argikar, Upendra (2018) Models and approaches describing metabolism, transport, and toxicity of drugs administered by the ocular route. Drug metabolism and disposition, 46. pp. 1670-1683. ISSN 1521-009X

Abstract

The eye is responsible for the sense of vision. It has evolved into a complex organ with a series of anatomical barriers, which provide protection from physical and chemical injury. These barriers are essential in maintaining homeostasis and function of the eye. The physiology of the eye is also complex with dynamic flows and clearance mechanisms. A variety of novel in vitro, in vivo, and ex vivo experimental models aimed at studying ocular drug metabolism and disposition have been reported in the literature. Several studies document the use of laboratory animals for the prediction of ocular pharmacokinetics in man. While no one system is perfect, many are useful in combination. This review focuses on the use of human-relevant and human-derived models which can be utilized in discovery and development to understand ocular disposition of new chemical entities. Benefits and caveats of each model are discussed. Furthermore, absorption, distribution, metabolism, and excretion (ADME) case studies are also summarized in a retrospective manner. Finally, a discussion on the novel technologies and a hypothesis driven ocular drug classification system, provide a holistic perspective on ADME properties of drugs administered by the ocular route.

Item Type: Article
Keywords: Eye, ocular drug metabolism, ocular drug transport, ocular pharmacokinetics, melanin, ADME, accelerator mass spectrometry, CyTOF, MALDI IMS
Date Deposited: 22 Jan 2019 00:45
Last Modified: 22 Jan 2019 00:45
URI: https://oak.novartis.com/id/eprint/36775

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