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Bioequivalence of fixed‐dose combinations of dapagliflozin and metformin with single‐component tablets in healthy subjects and the effect of food on bioavailability
Author(s) -
de Bruin Tjerk W.A.,
Reele Stots,
HamerMaansson Jennifer E.,
Parikh Shamik,
Tang Weifeng
Publication year - 2015
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.220
Subject(s) - dapagliflozin , bioequivalence , metformin , medicine , bioavailability , pharmacokinetics , meal , area under the curve , fixed dose combination , pharmacology , endocrinology , type 2 diabetes , insulin , diabetes mellitus
Abstract The pharmacokinetics (PK) of dapagliflozin and metformin administered as fixed‐dose combination (FDC) tablets (2.5 mg dapagliflozin/850 mg metformin or 5 mg dapagliflozin/1000 mg metformin) or as separate tablets in healthy subjects were evaluated in 2 separate studies. Study 1 evaluated PK by measuring mean ratios of area under the plasma concentration–time curve (time zero to infinity [AUC inf ]), AUC from zero to time of last measurable concentration (AUC 0–t ), and maximum observed plasma concentration (C max ) for single‐component or FDC tablets following a non‐high‐fat meal. Mean ratios of AUC inf , AUC 0–t , and C max for FDC or single‐component dapagliflozin and metformin tablets were close to unity. In study 2, AUC inf , AUC 0–t , and C max for the FDC tablet were obtained fasting and after a high‐fat meal. Dapagliflozin 5 mg and metformin 1000 mg geometric mean C max was increased in the fasted versus fed state (61.9 vs 43.9 and 1600 vs 1330 ng/mL, respectively), but AUC 0–t was similar (267 and 265 and 11 000 and 10 600 ng · h/mL, respectively). In summary, FDC tablets were bioequivalent to single‐component tablets, and total absorption (AUC) was similar for non‐high‐fat and high‐fat meals.