title: 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.
authors.affiliation: Global Medicines Department, AstraZeneca, Gaithersburg, MD, USA.
authors.forename: Tjerk W A
authors.initials: TW
authors.lastname: de Bruin
authors.affiliation: Reele Consulting, LLC, Scottsville, VA, USA.
authors.forename: Stots
authors.initials: S
authors.lastname: Reele
authors.affiliation: Global Medicines Department, AstraZeneca, Wilmington, DE, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Hamer-Maansson
authors.affiliation: Global Medicines Department, AstraZeneca, Gaithersburg, MD, USA.
authors.forename: Shamik
authors.initials: S
authors.lastname: Parikh
authors.affiliation: Global Medicines Department, AstraZeneca, Gaithersburg, MD, USA.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Tang
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D018592:Cross-Over Studies; D004338:Drug Combinations; D005215:Fasting; D005260:Female; D018565:Food-Drug Interactions; D005960:Glucosides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008875:Middle Aged; D013607:Tablets; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D004338:Drug Combinations; D005960:Glucosides; D007004:Hypoglycemic Agents; D013607:Tablets; C529054:dapagliflozin; D008687:Metformin
keywords: SGLT2 inhibitor; dapagliflozin; fixed-dose combination; metformin; pharmacokinetics