Do We Need to Study Metabolism and Distribution in the Eye: Why, When, and Are We There Yet?
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.
Analytical Sciences and Imaging, Biotransformation Group, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts 02139. Electronic address: upendra.argikar@novartis.com.
Upendra A
UA
Argikar
Analytical Sciences and Imaging, Biotransformation Group, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts 02139.
Jennifer L
JL
Dumouchel
Analytical Sciences and Imaging, Biotransformation Group, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts 02139.
Valerie M
VM
Kramlinger
Analytical Sciences and Imaging, Biotransformation Group, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts 02139.
Amanda L
AL
Cirello
Analytical Sciences and Imaging, Biotransformation Group, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts 02139.
Mithat
M
Gunduz
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523.
Christine E
CE
Dunne
Analytical Sciences and Imaging, Biotransformation Group, Novartis Institutes for BioMedical Research, Basel, Switzerland.
Bindi
B
Sohal
D060433:Administration, Ophthalmic; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods; D005123:Eye / Q000378:metabolism*; D006801:Humans; D009883:Ophthalmic Solutions / Q000493:pharmacokinetics*
D009883:Ophthalmic Solutions
disease state; drug development; drug discovery; drug-metabolizing enzymes; in vitro models; melanin binding; ocular metabolism; ophthalmic drug delivery