title: Effect of food on the pharmacokinetics of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, and assessment of dose proportionality in healthy volunteers.
abstract: OBJECTIVE
  Empagliflozin is an orally available, potent and highly selective inhibitor of the sodium glucose cotransporter 2 (SGLT2). This study was undertaken to investigate the effect of food on the pharmacokinetics of 25 mg empagliflozin and to assess dose proportionality between 10 mg and 25 mg empagliflozin under fasted conditions.
  
  
  METHODS
  In this open-label, 3-way, cross-over study, 18 healthy volunteers received 3 single doses of empagliflozin in a randomized sequence (25 mg empagliflozin under fasted conditions, 25 mg empagliflozin after a high-fat, high-calorie breakfast and 10 mg empagliflozin under fasted conditions), each separated by a washout period of at least 7 days. Serial plasma samples were collected at selected time points over a period of 72 hours.
  
  
  RESULTS
  Administration with food had no clinically relevant effect on the area under the plasma concentration-time curve (AUC0-∞) of empagliflozin (geometric mean ratio (GMR): 84.04, 90% confidence interval (CI): 80.86 - 87.34). The decrease observed in the maximum plasma concentrations (Cmax) of empagliflozin (GMR: 63.22, 90% CI: 56.74 - 70.44) when administered with food was not considered clinically meaningful. The increases in AUC0-∞ and Cmax for 10 mg vs. 25 mg empagliflozin administered under fasting conditions were roughly dose-proportional, as demonstrated by the slope β of the regression lines being slightly less than 1 (slope β for AUC0-∞: 0.94, 95% CI: 0.90 - 0.97; slope β for Cmax: 0.91, 95% CI: 0.80 - 1.01). Empagliflozin was well tolerated under fed and fasting conditions.
  
  
  CONCLUSIONS
  The results support administration of empagliflozin tablets independently of food. Increases in empagliflozin exposure under fasting conditions were roughly dose-proportional between 10 mg and 25 mg empagliflozin.
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, and Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: Sreeraj
authors.initials: S
authors.lastname: Macha
authors.forename: Arvid
authors.initials: A
authors.lastname: Jungnik
authors.forename: Kathrin
authors.initials: K
authors.lastname: Hohl
authors.forename: Dagmar
authors.initials: D
authors.lastname: Hobson
authors.forename: Afshin
authors.initials: A
authors.lastname: Salsali
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Woerle
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D005260:Female; D018565:Food-Drug Interactions; D005960:Glucosides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C570240:empagliflozin