title: Pharmacokinetic and pharmacodynamic study of ipragliflozin in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled study.
abstract: OBJECTIVE
  Ipragliflozin is a novel and highly selective sodium-glucose transporter 2 (SGLT2) inhibitor that reduces plasma glucose levels by enhancing urinary glucose excretion in patients with type 2 diabetes mellitus (T2DM). We examined the pharmacokinetic and pharmacodynamic characteristics of two oral doses of ipragliflozin in Japanese patients with T2DM.
  
  
  METHODS
  In this randomized, placebo-controlled, double-blind study, patients were treated with placebo, 50mg or 100mg ipragliflozin once daily for 14 days. Plasma and urine pharmacodynamic parameters were measured on Days -1 and 14, and pharmacokinetic parameters on Day 14. Pharmacodynamic characteristics included area under the curve (AUC) for plasma glucose and insulin for 0-3h (AUC0-3h) and 0-24h (AUC0-24h). Pharmacokinetic characteristics included AUC0-24h, maximum ipragliflozin concentration (Cmax), and time to maximum plasma ipragliflozin concentration (tmax).
  
  
  RESULTS
  Thirty patients were enrolled; 28 were included in pharmacokinetic/pharmacodynamic analyses and 30 in safety analyses. Administration of 50 and 100mg ipragliflozin significantly reduced fasting plasma glucose, as well as the AUC0-3h and AUC0-24h for plasma glucose relative to placebo. Both doses of ipragliflozin also reduced AUC0-24h for insulin, body weight, and glycoalbumin, while urinary glucose excretion increased remarkably. Cmax and AUC0-24h were 1.7- and 1.9-fold higher, respectively, in the 100-mg group than in the 50-mg group.
  
  
  CONCLUSIONS
  Ipragliflozin increased urinary glucose excretion and improved fasting and postprandial glucose, confirming its pharmacokinetic/pharmacodynamic properties in Japanese patients with T2DM.
authors.affiliation: Astellas Pharma Inc. Japan, Tokyo, Japan. Electronic address: takeshi.kadokura@astellas.com.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kadokura
authors.affiliation: Astellas Pharma Inc. Japan, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Akiyama
authors.affiliation: Shiga University of Medical Science, Shiga, Japan.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.affiliation: Astellas Pharma Inc. Japan, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Utsuno
authors.affiliation: Astellas Pharma Inc. Japan, Tokyo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kazuta
authors.affiliation: Astellas Pharma Inc. Japan, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Astellas Pharma Inc. Japan, Tokyo, Japan.
authors.forename: Itsuro
authors.initials: I
authors.lastname: Nagase
authors.affiliation: Astellas Pharma Global Development Europe, Leiden, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Smulders
authors.affiliation: The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kageyama
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D044466:Asian People; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005960:Glucosides / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D013876:Thiophenes / Q000493:pharmacokinetics* / Q000494:pharmacology*; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; D013876:Thiophenes; C572941:ipragliflozin
keywords: Fasting glucose; Ipragliflozin; Postprandial glucose; SGLT2; Type 2 diabetes