title: Impact of voglibose on the pharmacokinetics of dapagliflozin in Japanese patients with type 2 diabetes.
abstract: BACKGROUND
  Dapagliflozin is an orally administered selective sodium-glucose cotransporter 2 (SGLT2) inhibitor under development for the treatment of type 2 diabetes mellitus (T2DM). Dapagliflozin lowers blood glucose through a reduction in renal glucose reabsorption. This study was performed to assess the effect of the oral antidiabetic agent voglibose [0.2 mg thrice daily (t.i.d.)] at steady-state, on the pharmacokinetics, safety and tolerability of dapagliflozin administered as a single oral dose (10 mg) to Japanese patients with T2DM.
  
  
  METHODS
  This was an open-label, multi-center, drug-drug interaction study. A single oral dose of dapagliflozin (10 mg) was administered to 22 Japanese patients with T2DM in the presence and absence of voglibose (0.2 mg t.i.d.). Serial blood samples were collected before and at regular prespecified intervals after each dapagliflozin dose to determine dapagliflozin plasma concentrations and to evaluate pharmacokinetic parameters. Based on a mixed effect analysis of variance model, including the dosing condition as a fixed effect and patients as a random effect, the ratios of geometric means of area under curve from time 0 to infinity (AUC0-inf) and maximum observed plasma concentration (C max) with and without voglibose were estimated along with two-sided 90% confidence intervals (CIs).
  
  
  RESULTS
  In Japanese patients with T2DM, the exposure to dapagliflozin following a single oral dose of dapagliflozin 10 mg was not influenced by the concomitant administration of voglibose (0.2 mg t.i.d.). The geometric ratio (90% CI) for dapagliflozin AUC0-inf with/without voglibose was 1.009 (0.954, 1.067), and for C max 1.040 (0.899, 1.204). The median time to C max (t max) and plasma clearance of dapagliflozin were also similar between treatments. The mean half-life (t ½) for dapagliflozin was slightly higher when administered in combination with voglibose. Dapagliflozin 10 mg was well tolerated when administered alone and in combination with voglibose in Japanese patients with T2DM.
  
  
  CONCLUSIONS
  The results presented here support the co-administration of dapagliflozin and voglibose without dose adjustment of either agent.
authors.affiliation: Moriya Keiyu Hospital, 980-1, Tatuzawa, Moriya City, Ibaraki, 302-0118, Japan, imamura.akira@keiyu.or.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Imamura
authors.forename: Masahito
authors.initials: M
authors.lastname: Kusunoki
authors.forename: Shinya
authors.initials: S
authors.lastname: Ueda
authors.forename: Nobuya
authors.initials: N
authors.lastname: Hayashi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Imai