Title: Pharmacokinetics and pharmacodynamics of dapagliflozin, a novel selective inhibitor of sodium-glucose co-transporter type 2, in Japanese subjects without and with type 2 diabetes mellitus
Abstract: Diabetes, Obesity and MetabolismVolume 13, Issue 4 p. 357-365 Pharmacokinetics and pharmacodynamics of dapagliflozin, a novel selective inhibitor of sodium–glucose co-transporter type 2, in Japanese subjects without and with type 2 diabetes mellitus S. Kasichayanula, Corresponding Author S. Kasichayanula Bristol-Myers Squibb Company, Princeton, NJ, USASreeneeranj Kasichayanula, R&D, Bristol-Myers Squibb Company, PO Box 4000, Rt 206 and Province Line Road, Princeton, NJ 08543-4000, USA.E-mail: [email protected]Search for more papers by this authorM. Chang, M. Chang Bristol-Myers Squibb Company, Princeton, NJ, USASearch for more papers by this authorM. Hasegawa, M. Hasegawa Bristol-Myers Squibb Company, Shinjuku, Tokyo, JapanSearch for more papers by this authorX. Liu, X. Liu Bristol-Myers Squibb Company, Princeton, NJ, USASearch for more papers by this authorN. Yamahira, N. Yamahira Bristol-Myers Squibb Company, Shinjuku, Tokyo, JapanSearch for more papers by this authorF. P. LaCreta, F. P. LaCreta Bristol-Myers Squibb Company, Princeton, NJ, USASearch for more papers by this authorY. Imai, Y. Imai Bristol-Myers Squibb Company, Shinjuku, Tokyo, JapanSearch for more papers by this authorD. W. Boulton, D. W. Boulton Bristol-Myers Squibb Company, Princeton, NJ, USASearch for more papers by this author S. Kasichayanula, Corresponding Author S. Kasichayanula Bristol-Myers Squibb Company, Princeton, NJ, USASreeneeranj Kasichayanula, R&D, Bristol-Myers Squibb Company, PO Box 4000, Rt 206 and Province Line Road, Princeton, NJ 08543-4000, USA.E-mail: [email protected]Search for more papers by this authorM. Chang, M. Chang Bristol-Myers Squibb Company, Princeton, NJ, USASearch for more papers by this authorM. Hasegawa, M. Hasegawa Bristol-Myers Squibb Company, Shinjuku, Tokyo, JapanSearch for more papers by this authorX. Liu, X. Liu Bristol-Myers Squibb Company, Princeton, NJ, USASearch for more papers by this authorN. Yamahira, N. Yamahira Bristol-Myers Squibb Company, Shinjuku, Tokyo, JapanSearch for more papers by this authorF. P. LaCreta, F. P. LaCreta Bristol-Myers Squibb Company, Princeton, NJ, USASearch for more papers by this authorY. Imai, Y. Imai Bristol-Myers Squibb Company, Shinjuku, Tokyo, JapanSearch for more papers by this authorD. W. Boulton, D. W. Boulton Bristol-Myers Squibb Company, Princeton, NJ, USASearch for more papers by this author First published: 12 January 2011 https://doi.org/10.1111/j.1463-1326.2011.01359.xCitations: 80Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract Aims: Dapagliflozin, a selective, orally active inhibitor of the renal sodium–glucose co-transporter type 2 (SGLT2) is in development for the treatment of type 2 diabetes mellitus (T2DM). Here, the pharmacokinetics (PK) and pharmacodynamics (PD) of dapagliflozin were evaluated in healthy Japanese subjects and in Japanese subjects with T2DM. Methods: Two studies were conducted: a single-ascending dose (SAD) study (2.5–50 mg) in 32 healthy subjects and a multiple-ascending dose (MAD) study (2.5–20 mg QD for 14 days) in 36 subjects with T2DM. Safety and tolerability were assessed in both studies. Single and multiple dose PK of dapagliflozin and its inactive major metabolite, dapagliflozin 3-O-glucuronide, and PD (urinary glucose parameters) were characterized. Plasma glucose parameters were assessed over 14 days in the MAD study. Results: No serious adverse events or discontinuations due to adverse events occurred in either study. In healthy and T2DM subjects, dapagliflozin was rapidly absorbed with a time to maximum plasma concentration of 0.5–1.3 h. Systemic exposure of dapagliflozin and dapagliflozin 3-O-glucuronide, measured by maximum plasma concentration and area under the plasma concentration–time curve, increased proportional to dose. On a molar basis, systemic exposure to dapagliflozin 3-O-glucuronide was similar to parent dapagliflozin. There was a dose-related increase in the amount of glucose excreted in the urine (SAD and MAD), which was associated with dose-related decreases in plasma glucose parameters in subjects with T2DM (MAD). Conclusions: Dapagliflozin was well tolerated and showed predictable dose-proportional PK and PD parameters in both healthy and T2DM Japanese subjects. References 1 IDF Diabetes Atlas. International Diabetes Federation. Diabetes and impaired glucose tolerance. 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Population pharmacokinetic analysis of dapagliflozin in healthy subjects and patients with type 2 diabetes mellitus. Clin Pharmacol Ther 2010; 83: S93. Citing Literature Volume13, Issue4April 2011Pages 357-365 ReferencesRelatedInformation
Publication Year: 2011
Publication Date: 2011-02-23
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 98
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