title: No pharmacokinetic interaction between ipragliflozin and sitagliptin, pioglitazone, or glimepiride in healthy subjects.
abstract: OBJECTIVE
  To investigate the effect of ipragliflozin on the pharmacokinetics of sitagliptin, pioglitazone or glimepiride and vice versa in healthy subjects.
  
  
  METHODS
  Three trials with an open-label, randomized, two-way crossover design were conducted in healthy subjects. Ipragliflozin 150 mg, sitagliptin 100 mg, pioglitazone 30 mg or glimepiride 1-2 mg were administered alone or in combination. Primary endpoints were the area under the curve from the time of dosing to infinity (AUC(inf)) and the maximum observed plasma concentration (C(max)) of each drug.
  
  
  RESULTS
  Multiple doses of ipragliflozin did not change the AUC(inf) and C(max) of a single dose of sitagliptin, pioglitazone or glimepiride. All geometric mean ratios and 90% CIs for AUC(inf) and C(max) , with and without ipragliflozin, were within the predefined range of 80-125% (AUC(inf) : sitagliptin 100.1 [96.9-103.5], pioglitazone 101.7 [96.6-107.0], glimepiride 105.1 [101.3-109.0], and C(max) : sitagliptin 92.4 [82.8-103.1], pioglitazone 98.6 [87.7-110.8], glimepiride 110.0 [101.9-118.8]). Similarly, multiple doses of sitagliptin, pioglitazone or glimepiride did not change the pharmacokinetics of a single dose of ipragliflozin (AUC(inf) : 95.0 [93.4-103.1], 100.0 [98.1-102.0], 99.1 [96.6-101.6]; and C(max) : 96.5 [90.4-103.1], 93.5 [86.3-101.2], 97.3 [89.2-106.2]). Ipragliflozin either alone or in combination with any of the three glucose-lowering drugs was well tolerated in healthy subjects.
  
  
  CONCLUSIONS
  Ipragliflozin did not affect the pharmacokinetics of sitagliptin, pioglitazone or glimepiride and vice versa, suggesting that no dose-adjustments are likely to be required when ipragliflozin is given in combination with other glucose-lowering drugs in patients with type 2 diabetes mellitus.
authors.affiliation: Global Clinical Pharmacology and Exploratory Development, Astellas Pharma Europe BV, Leiderdorp, The Netherlands. Ronald.Smulders@eu.astellas.com
authors.forename: R A
authors.initials: RA
authors.lastname: Smulders
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: S A
authors.initials: SA
authors.lastname: Veltkamp
authors.forename: J
authors.initials: J
authors.lastname: van Dijk
authors.forename: W J J
authors.initials: WJ
authors.lastname: Krauwinkel
authors.forename: J
authors.initials: J
authors.lastname: Keirns
authors.forename: T
authors.initials: T
authors.lastname: Kadokura
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D015992:Body Mass Index; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005960:Glucosides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D011719:Pyrazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000068900:Sitagliptin Phosphate; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013876:Thiophenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D005960:Glucosides; D007004:Hypoglycemic Agents; D011719:Pyrazines; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D013876:Thiophenes; D014230:Triazoles; C572941:ipragliflozin; C057619:glimepiride; D000068900:Sitagliptin Phosphate; D000077205:Pioglitazone