RT Journal Article
SR Electronic
T1 Pharmacokinetics and Pharmacodynamics of the SGLT2 Inhibitor Remogliflozin Etabonate in Subjects with Mild and Moderate Renal Impairment
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1077
OP 1083
DO 10.1124/dmd.114.062828
VO 43
IS 7
A1 Robin O’Connor-Semmes
A1 Susan Walker
A1 Anita Kapur
A1 Elizabeth K. Hussey
A1 June Ye
A1 Laurene Wang-Smith
A1 Wenli Tao
A1 Robert L. Dobbins
A1 Bentley Cheatham
A1 William O. Wilkison
YR 2015
UL http://dmd.aspetjournals.org/content/43/7/1077.abstract
AB Remogliflozin etabonate (RE), the prodrug of remogliflozin, is an inhibitor of the sodium glucose–dependent renal transporter 2 (SGLT2), enabling urinary glucose excretion to reduce hyperglycemia for the treatment of type 2 diabetes. Renal function declines more rapidly in patients with type 2 diabetes, making it difficult or unsafe to continue on some antidiabetic therapeutics. In an initial effort to understand the potential utility of RE in patients with renal impairment, the pharmacodynamics and pharmacokinetics of RE were evaluated in a single oral dose (250 mg) in patients with renal impairment as compared with control subjects. As shown by pharmacodynamic measurements of urinary glucose excretion, there was no clinically significant reduction in the ability of remogliflozin to inhibit SGLT2. In addition, there were no significant changes in area under the curve (from 0 to infinity) or half-life of remogliflozin, suggesting renal impairment does not alter the pharmacokinetics of remogliflozin. In contrast to other SGLT2 inhibitors which accumulate in patients with renal impairment, adjustment of the dosage of RE in subjects with mild or moderate renal impairment is not indicated based on the observations in this study.