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Dapagliflozin twice daily or once daily: effect on pharmacokinetics and urinary glucose excretion in healthy subjects
Author(s) -
Tang W.,
Reele S.,
HamerMaansson J. E.,
Parikh S.,
de Bruin T. W. A.
Publication year - 2015
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12425
Subject(s) - dapagliflozin , urine , pharmacokinetics , excretion , urinary system , crossover study , endocrinology , chemistry , medicine , reabsorption , kidney , diabetes mellitus , type 2 diabetes , placebo , alternative medicine , pathology
The primary objective of this single‐centre, open‐label crossover study ( NCT01072578 ) was to assess the effect of dapagliflozin on the amount of glucose in the blood and urine in healthy volunteers when dapagliflozin was administered once a day (10 mg) versus twice a day (5 mg every 12 h) after 5 days of dosing. At steady state, the AUC ss (0‐24) (area under the dapagliflozin curve (0‐24 hours) at steady state), C ss, av (average concentration at steady state) between dapagliflozin 5 mg twice daily and 10 mg once daily were similar AUC ss(0‐24) [5 mg bid, (458.0 (28.7)) and 10 mg qd, (470.0 (28.5))] and C ss, av [5 mg bid 18.8 (28.9)) and 10 mg qd, (19.6(28.5))], but minimum and maximum plasma levels of dapagliflozin differed significantly. Percent inhibition of renal glucose reabsorption (% IRGRA ) and total urinary glucose excretion over 24 h were similar for both doses. The relationship between the mean dapagliflozin concentration and % IRGRA and the total urinary glucose excreted was well described by a maximum effect model. The results indicate that dapagliflozin may be used for either once daily or twice daily administration.