title: Pharmacokinetics of empagliflozin, a sodium glucose cotransporter 2 inhibitor, and simvastatin following co-administration in healthy volunteers.
abstract: OBJECTIVE
  This study was undertaken to investigate potential drugdrug interactions between the sodium glucose cotransporter 2 inhibitor empagliflozin and simvastatin.
  
  
  METHODS
  In this open-label, randomized crossover trial, healthy volunteers (median (range) age 36.5 (20 - 50) years) received 3 single-dose treatments: 25 mg empagliflozin (n = 18), 40 mg simvastatin (n = 17), and 25 mg empagliflozin with 40 mg simvastatin (n = 18).
  
  
  RESULTS
  Based on standard criteria, simvastatin had no effect on empagliflozin area under the plasma concentration-time curve (AUC(0-∞), adjusted geometric mean ratio (GMR): 102.05; 90% CI: 98.90 - 105.29) or maximum plasma concentration (C(max), GMR: 109.49; 90% CI: 96.91 - 123.69). There were only minor deviations in simvastatin AUC(0-∞) (GMR: 101.26; 90% CI: 80.06 - 128.07) and C(max) (GMR: 97.18; 90% CI: 76.30 - 123.77) when co-administered with empagliflozin. Empagliflozin had no effect on AUC(0-∞) (GMR: 104.87; 90% CI: 90.09 - 122.07) or C(max) (GMR: 97.27; 90% CI: 84.90 - 111.44) of simvastatin acid, the active metabolite of simvastatin. Adverse events (AEs) were reported for 6 subjects on empagliflozin, 4 on simvastatin, and 5 on co-administered treatment. No serious AEs or investigator-defined drug-related AEs were reported.
  
  
  CONCLUSIONS
  No relevant drug-drug interaction was observed, and pharmacokinetic results suggest that no dose adjustments for either drug are necessary when empagliflozin and simvastatin are co-administered. Empagliflozin was well tolerated when administered alone or in combination with simvastatin.
authors.forename: Sreeraj
authors.initials: S
authors.lastname: Macha
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lang
authors.forename: Sabine
authors.initials: S
authors.lastname: Pinnetti
authors.forename: Uli C
authors.initials: UC
authors.lastname: Broedl
mesh_terms: D000328:Adult; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D005960:Glucosides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C063287:simvastatin acid; D019821:Simvastatin; C570240:empagliflozin