Ocular cytochrome P450s and transporters: roles in disease and endobiotic and xenobiotic disposition

Drug Metab Rev. 2014 Aug;46(3):247-60. doi: 10.3109/03602532.2014.921190. Epub 2014 May 26.

Abstract

Drug metabolism and transport processes in the liver, intestine and kidney that affect the pharmacokinetics and pharmacodynamics of therapeutic agents have been studied extensively. In contrast, comparatively little research has been conducted on these topics as they pertain to the eye. Recently, however, catalytic functions of ocular cytochrome P450 enzymes have gained increasing attention, in large part due to the roles of CYP1B1 and CYP4V2 variants in primary congenital glaucoma and Bietti's corneoretinal crystalline dystrophy, respectively. In this review, we discuss challenges to ophthalmic drug delivery, including Phase I drug metabolism and transport in the eye, and the role of three specific P450s, CYP4B1, CYP1B1 and CYP4V2 in ocular inflammation and genetically determined ocular disease.

Keywords: CYP1B1; CYP4B1; CYP4V2; cytochrome P450; drug metabolism; drug transporters; genetic eye disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cytochrome P-450 Enzyme System / metabolism*
  • Eye / metabolism*
  • Eye Diseases / metabolism*
  • Humans
  • Metabolic Detoxication, Phase I / physiology
  • Xenobiotics / metabolism*

Substances

  • Xenobiotics
  • Cytochrome P-450 Enzyme System