title: Effect of Ipragliflozin (ASP1941), a novel selective sodium-dependent glucose co-transporter 2 inhibitor, on urinary glucose excretion in healthy subjects.
abstract: BACKGROUND
  Hyperglycaemia is associated with serious complications, significant morbidity and death. Despite the availability of a wide range of therapeutic options, many patients with diabetes mellitus fail to achieve or maintain recommended glycaemic goals. Ipragliflozin (ASP1941) is a novel, selective inhibitor of the sodium-dependent glucose co-transporter 2, which is highly expressed in the proximal tubules of the kidneys. It suppresses renal glucose reabsorption and increases urinary glucose excretion (UGE), potentially providing an insulin-independent treatment option for type 2 diabetes.
  
  
  METHODS
  This multiple ascending-dose study assessed the safety, tolerability, pharmacokinetics and pharmacodynamics of ipragliflozin in healthy subjects after single doses and multiple once-daily doses for 10 days (dose levels: 5-600 mg).
  
  
  RESULTS
  Ipragliflozin was well tolerated following single and multiple once-daily oral dosing. Ipragliflozin was rapidly absorbed with a median time to reach the maximum plasma concentration of 1.3 hours after the last dose. The area under the plasma concentration-time curve increased proportionally with increasing dose. The mean elimination half-life was 12 hours following the last dose. Ipragliflozin dose dependently increased UGE up to a maximum of approximately 59 g (327 mmol) of glucose excreted over 24 hours following multiple doses, without affecting plasma glucose levels in healthy subjects.
  
  
  CONCLUSIONS
  Administration of ipragliflozin was well tolerated and resulted in a rapid, dose-dependent increase in glucosuria. Pharmacodynamic and pharmacokinetic data suggest that ipragliflozin is suitable for prolonged once-daily oral treatment.
authors: Astellas Pharma Europe BV, Leiderdorp, the Netherlands. Sander.Veltkamp@eu.astellas.com
authors: Stephan A
authors: SA
authors: Veltkamp
authors: Takeshi
authors: T
authors: Kadokura
authors: Walter J J
authors: WJ
authors: Krauwinkel
authors: Ronald A
authors: RA
authors: Smulders
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000502:physiology; D001795:Blood Pressure Determination; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000378:metabolism; D005960:Glucosides / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D006029:Glycosuria / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012737:Sex Factors; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D027981:Symporters / Q000502:physiology; D013876:Thiophenes / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; D010919:Placebos; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D027981:Symporters; D013876:Thiophenes; C572941:ipragliflozin; D005947:Glucose