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Do We Need to Study Metabolism and Distribution in the Eye: Why, When, and Are We There Yet?

Argikar, Upendra and Dumouchel, Jennifer and Kramlinger, Valerie and Cirello, Amanda and Gunduz, Mithat and Dunne, Christine and Sohal, Bindi (2017) Do We Need to Study Metabolism and Distribution in the Eye: Why, When, and Are We There Yet? Journal of Pharmaceutical Sciences, 106 (9). pp. 2276-2281. ISSN 15206017

Abstract

The liver is known to be the principal site of drug metabolism. Depending on the route of administration, especially in cases of topical and local delivery, evaluation of local drug metabolism in extrahepatic tissues is vital to assess fraction of the drug metabolized. This parameter becomes important from the point of view of drug availability or the contribution to overall clearance. Examples include fraction metabolized in the gut for oral drugs and contribution of pulmonary or renal clearance to total clearance of a drug. Diseases of the eye represent a rising unmet medical need and a number of therapeutics are currently being developed in the form of small molecules and biologics. Treatment of ocular diseases has expanded to explore various topical formulations and local short- and long-term therapies by ocular routes of administration. Until recently, metabolism in the eye for any species, including human, was not well documented, but this topic is gaining wide interest. Many in vitro-ex vivo models, each with separate pros and cons, are being used for studying ocular metabolism. This review is aimed at providing a perspective on the relevance and application of ocular metabolism, melanin binding, and the use of tissue- and cell-derived ocular models in discovery and preclinical development.

Item Type: Article
Keywords: Disease state Drug development Drug discovery Drug-metabolizing enzymes in vitro models Melanin binding Ocular metabolism Ophthalmic drug delivery
Date Deposited: 05 Sep 2017 00:45
Last Modified: 25 Jan 2019 00:45
URI: https://oak.novartis.com/id/eprint/31957

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