Abstract:
:Remogliflozin etabonate (RE) is the prodrug of remogliflozin (R), an inhibitor of renal glucose transport designed to reduce blood glucose concentrations for the treatment of type 2 diabetes. This open-label, randomized, single-dose, four-way crossover study, (with one add-on arm) in eight healthy men evaluated the regional gastrointestinal absorption of RE, the systemic appearance of the active entity R, and an active metabolite, GSK279782. The InteliSite(®) Companion Capsule was used to administer a single dose of RE 100 mg to the mid-small intestine or cecum/colon. Oral administration of the IR tablet of RE showed similar bioavailability of R compared with small intestine delivery with both suspension and solution. The lowest bioavailability of remogliflozin was found with large intestine delivery and therefore not a suitable region for prodrug delivery. Although both lower permeability and decreased ester hydrolysis of remogliflozin etabonate in the colon can explain reduced plasma exposures of remogliflozin, the data suggest relatively limited remogliflozin etabonate hydrolysis in the colon and provides evidence for a diminishing gradient of esterase activity from small to large intestine.
journal_name
Biopharm Drug Disposjournal_title
Biopharmaceutics & drug dispositionauthors
O'Connor-Semmes RL,Sandefer EP,Hussey EK,Tao W,Doll WJ,Page RC,Dobbins Rdoi
10.1002/bdd.1824subject
Has Abstractpub_date
2013-03-01 00:00:00pages
79-86issue
2eissn
0142-2782issn
1099-081Xjournal_volume
34pub_type
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