An in vitro approach to investigate ocular metabolism of a topical, selective β1-adrenergic blocking agent, betaxolol. (May 2015)

• Record Type: Journal Article
• Authors: Bushee, Jennifer L.; Dunne, Christine E.; Argikar, Upendra A.
• Is Part Of: Xenobiotica. Volume 45:Number 5(2015:May)
• Page Start: 396
• Page End: 405
• Publication Date: 2015-05
• Subjects: Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.3109/00498254.2014.987191
• Languages: English
• ISSNs: 0049-8254

Abstract

<abstract> <title>Abstract</title> <p>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.</p> <p>2. <italic>In vitro</italic> ocular fractions indicated the formation of an active metabolite, across rat, rabbit and human, which was only observed historically in the liver.</p> <p>3. Ocular metabolic profiles of preclinical toxicology species, rat and rabbit, were not predictive of human <italic>in vitro</italic> ocular data. M1 was specific to human and only captured by the liver data.</p> <p>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.</p> <p>5. This research assesses <italic>in vitro</italic> species and organ differences across preclinical species and human. The complex data set highlights the need for an <italic>in vitro</italic> ocular system to explore poorly documented ocular metabolism.</p> </abstract>