Bioequivalence of fixed-dose combinations of dapagliflozin and metformin with single-component tablets in healthy subjects and the effect of food on bioavailability.

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 [AUCinf ]), AUC from zero to time of last measurable concentration (AUC0-t ), and maximum observed plasma concentration (Cmax ) for single-component or FDC tablets following a non-high-fat meal. Mean ratios of AUCinf , AUC0-t , and Cmax for FDC or single-component dapagliflozin and metformin tablets were close to unity. In study 2, AUCinf , AUC0-t , and Cmax for the FDC tablet were obtained fasting and after a high-fat meal. Dapagliflozin 5 mg and metformin 1000 mg geometric mean Cmax was increased in the fasted versus fed state (61.9 vs 43.9 and 1600 vs 1330 ng/mL, respectively), but AUC0-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.