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- Title
Dapagliflozin, a novel SGLT2 inhibitor, induces dose-dependent glucosuria in healthy subjects.
- Authors
Komoroski, B; Vachharajani, N; Boulton, D; Kornhauser, D; Geraldes, M; Li, L; Pfister, M
- Abstract
Dapagliflozin selectively inhibits renal glucose reabsorption by inhibiting sodium-glucose cotransporter-2 (SGLT2). It was developed as an insulin-independent treatment approach for type 2 diabetes mellitus (T2DM). The safety, tolerability, pharmacokinetics, and pharmacodynamics of the drug were evaluated in single-ascending-dose (SAD; 2.5-500 mg) and multiple-ascending-dose (MAD; 2.5-100 mg daily for 14 days) studies in healthy subjects. Dapagliflozin exhibited dose-proportional plasma concentrations with a half-life of approximately 17 h. The amount of glucosuria was also dose-dependent. Cumulative amounts of glucose excreted on day 1, relating to doses from 2.5-100 mg (MAD), ranged from 18 to 62 g; day 14 values were comparable to day 1 values, with no apparent changes in glycemic parameters. Doses of approximately 20-50 mg provided close-to-maximal SGLT2 inhibition for at least 24 h. Dapagliflozin demonstrates pharmacokinetic (PK) characteristics and dose-dependent glucosuria that are sustained over 24 h, which indicates that it is suitable for administration in once-daily doses and suggests that further investigation of its efficacy in T2DM patients is warranted.
- Publication
Clinical pharmacology and therapeutics, 2009, Vol 85, Issue 5, p520
- ISSN
1532-6535
- Publication type
Journal Article
- DOI
10.1038/clpt.2008.251