An in vitro approach to investigate ocular metabolism of a topical, selective β1-adrenergic blocking agent, betaxolol

Xenobiotica. 2015 May;45(5):396-405. doi: 10.3109/00498254.2014.987191. Epub 2014 Dec 5.


1. Topical glaucoma treatments have often been limited by poor absorption and bioavailability. Betaxolol, a selective β1-blocker, has been well studied for its pharmacokinetics and disposition. Limited ocular, betaxolol metabolism data is available despite a growing number of novel ocular treatments. 2. In vitro ocular fractions indicated the formation of an active metabolite, across rat, rabbit and human, which was only observed historically in the liver. 3. Ocular metabolic profiles of preclinical toxicology species, rat and rabbit, were not predictive of human in vitro ocular data. M1 was specific to human and only captured by the liver data. 4. Liver S9 over predicted the extent of ocular metabolism compared to ocular fractions. Rabbit liver S9 fractions demonstrated extensive glucuronidation and higher parent turn-over in 1 h as compared to other matrices. 5. This research assesses in vitro species and organ differences across preclinical species and human. The complex data set highlights the need for an in vitro ocular system to explore poorly documented ocular metabolism.

Keywords: Active metabolite; S9 fraction; antiglaucoma; extrahepatic metabolism; high resolution mass spectrometry.

MeSH terms

  • Administration, Topical
  • Adolescent
  • Adrenergic beta-Antagonists / chemistry
  • Adrenergic beta-Antagonists / metabolism
  • Adrenergic beta-Antagonists / pharmacology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Betaxolol / chemistry
  • Betaxolol / metabolism
  • Betaxolol / pharmacology*
  • Chromatography, Liquid
  • Eye / drug effects*
  • Female
  • Humans
  • Male
  • Metabolomics
  • Middle Aged
  • Rabbits
  • Rats, Sprague-Dawley
  • Tandem Mass Spectrometry
  • Young Adult


  • Adrenergic beta-Antagonists
  • Betaxolol