title: Relative bioavailability of an empagliflozin 25-mg/linagliptin 5-mg fixed-dose combination tablet .
abstract: OBJECTIVE
  This relative bioavailability study compared a fixed-dose combination (FDC) tablet of empagliflozin 25 mg/linagliptin 5 mg with the corresponding individual components. In addition, the effect of food on the bioavailability of the FDC was studied, and the standard-dissolving formulation FDC was compared with a slow-dissolving side batch.
  
  
  METHODS
  An open-label, randomized, crossover study design was used (ClinicalTrials.gov Identifier NCT01189201). Healthy volunteers (n = 42) each received three single-dose treatments: FDC standard dissolution, individual tablets, and either FDC standard dissolution with food or FDC slow dissolution. Primary endpoints for relative bioavailability comparisons were area under the plasma concentration-time curve (AUC) over time 0 to the last time point with the plasma concentration above the quantification limit (AUC0-tz) for empagliflozin, AUC from 0 to 72 hours (AUC0-72) for linagliptin, and maximum plasma concentration (Cmax) for both drugs.
  
  
  RESULTS
  In all three comparisons, the 90% confidence intervals for the ratios of AUCs were within the standard acceptance range (80 - 125%) for bioequivalence. Empagliflozin and linagliptin both showed reductions in Cmaxafter food compared with the fasted state, although overall exposure remained similar. The empagliflozin/linagliptin combinations were well tolerated.
  
  
  CONCLUSIONS
  This study shows that the FDC of empagliflozin 25 mg/linagliptin 5 mg can be regarded as bioequivalent to the individual tablets. Administering the tablet after food or a tablet with a slow-dissolution profile did not have a clinically-relevant impact on the bioavailability of empagliflozin/linagliptin FDC tablets. .
authors.forename: Stephan
authors.initials: S
authors.lastname: Glund
authors.forename: Michaela
authors.initials: M
authors.lastname: Mattheus
authors.forename: Frank
authors.initials: F
authors.lastname: Runge
authors.forename: Peter
authors.initials: P
authors.lastname: Rose
authors.forename: Christian
authors.initials: C
authors.lastname: Friedrich
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D018592:Cross-Over Studies; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005260:Female; D005858:Germany; D005960:Glucosides / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D000069476:Linagliptin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D012995:Solubility; D013607:Tablets; D013810:Therapeutic Equivalency
chemical_list: D001559:Benzhydryl Compounds; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004338:Drug Combinations; D005960:Glucosides; D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013607:Tablets; D000069476:Linagliptin; C570240:empagliflozin