Anzeige
Erschienen in:
01.12.2011 | Original Research Article
Effect of Ipragliflozin (ASP1941), a Novel Selective Sodium-Dependent Glucose Co-Transporter 2 Inhibitor, on Urinary Glucose Excretion in Healthy Subjects
Erschienen in: Clinical Drug Investigation | Ausgabe 12/2011
Einloggen, um Zugang zu erhaltenAbstract
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.
Conclusion: 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.
Trial Registration: ClinicalTrials.gov Identifier: NCT01288898.