Ocular drug-metabolizing enzymes: focus on esterases

Abstract

This review describes current knowledge on the expression of ocular phase I and II drug-metabolizing enzymes in the main animal species used in ocular drug development and in humans, with a focus on ocular esterases and their prodrug substrates. The eye possesses a unique metabolic profile, exhibiting a lower and restricted expression of major cytochrome P450s (CYPs) and most transferases apart from glutathione S-transferases (GST) when compared to the liver. In contrast, hydrolytic enzymes are abundant in many ocular tissues. These enzymes have attracted interest because of their role in prodrug activation and drug elimination. A literature survey suggests profound variations in tissue expression levels and activities between different species but also points out significant gaps in knowledge. These uncertainties highlight a need for more detailed characterization of enzymes in individual ocular tissues and across species to aid future translational studies in ophthalmic drug research. Thus, an in-depth analysis of ocular drug metabolism and species differences is crucial for ocular drug development.

Keywords:

• Ocular drug delivery
• ocular tissues
• drug-metabolizing enzymes
• esterases
• ester prodrugs

Author contributions

Conceptualization, P.H. and A.H.; writing – original draft preparation, A.H. and P.H.; writing – review and editing, P.H. and A.H.; supervision, P.H.; funding acquisition, P.H. and A.H.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The studies from the Honkakoski Laboratory were supported by the EU-ITN project OCUTHER (H2020-MSCA-ITN-2016, Grant Number 722717). A.H. acknowledges the financial support from the Maud Kuistila Memorial Foundation, the Finnish Cultural Foundation, the Oskar Öflunds Foundation, and the Doctoral Programme in Drug Research at the University of Eastern Finland.