PMID- 25855342
OWN - NLM
STAT- MEDLINE
DCOM- 20160323
LR  - 20221207
IS  - 1865-8652 (Electronic)
IS  - 0741-238X (Print)
IS  - 0741-238X (Linking)
VI  - 32
IP  - 4
DP  - 2015 Apr
TI  - Pharmacokinetics, Pharmacodynamics, and Safety of Luseogliflozin in Japanese 
      Patients with Type 2 Diabetes Mellitus: A Randomized, Single-blind, 
      Placebo-controlled Trial.
PG  - 319-40
LID - 10.1007/s12325-015-0200-x [doi]
AB  - INTRODUCTION: Luseogliflozin, a potent, selective sodium glucose cotransporter 2 
      inhibitor, promotes urinary glucose excretion (UGE) and reduces plasma glucose 
      concentrations. Luseogliflozin was approved for use in Japan after favorable 
      pharmacokinetic, pharmacodynamic, and safety profiles were reported in healthy 
      Japanese subjects and patients with type 2 diabetes mellitus (T2DM) in clinical 
      development studies. We aimed to investigate the pharmacokinetics, 
      pharmacodynamics, and safety of multiple doses of luseogliflozin administered 
      once daily for 7 days in Japanese patients with T2DM. METHODS: We conducted a 
      randomized, placebo-controlled, single-blind, parallel-group, clinical 
      pharmacology study at the P-One Clinic, Keikokai Medical Corporation (Tokyo, 
      Japan) between August 2009 and November 2009. Forty Japanese patients with T2DM 
      were randomly assigned to receive once-daily 0.5, 1, 2.5 or 5 mg luseogliflozin 
      or placebo for 7 days. We assessed the pharmacokinetics, pharmacodynamics 
      (including changes in UGE and plasma glucose concentrations), and safety of 
      luseogliflozin. RESULTS: The plasma concentrations of luseogliflozin and its 
      active metabolite, M2, were dose proportional, without accumulation. 24-h UGE was 
      greater in all luseogliflozin groups versus placebo. Least-squares mean 
      differences in 24-h UGE on Day 7 increased dose dependently in the luseogliflozin 
      groups, with values of 49.2, 66.5, 89.4, and 101 g/day at 0.5, 1, 2.5, and 5 mg, 
      respectively. On Day 7, the areas under the concentration-time curves for 
      post-meal plasma glucose and the mean plasma glucose for 0-16 h were 
      significantly lower in all luseogliflozin groups versus placebo. Seven patients 
      had mild adverse events (AEs); all were resolved. No AEs led to study 
      discontinuation. CONCLUSION: Once-daily administration of luseogliflozin for 7 
      days increased 24-h UGE in a dose-dependent manner, reduced plasma glucose 
      concentrations, and was well tolerated in Japanese patients with T2DM. The 
      pharmacokinetic and pharmacodynamic profile of luseogliflozin observed in this 
      study supports its once-daily dosing regimen. FUNDING: Taisho Pharmaceutical Co., 
      Ltd.
FAU - Sasaki, Takashi
AU  - Sasaki T
AD  - Institute of Clinical Medicine and Research, The Jikei University School of 
      Medicine, 163-1 Kashiwashita, Kashiwa, Chiba, 277-8567, Japan.
FAU - Seino, Yutaka
AU  - Seino Y
FAU - Fukatsu, Atsushi
AU  - Fukatsu A
FAU - Ubukata, Michito
AU  - Ubukata M
FAU - Sakai, Soichi
AU  - Sakai S
FAU - Samukawa, Yoshishige
AU  - Samukawa Y
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150409
PL  - United States
TA  - Adv Ther
JT  - Advances in therapy
JID - 8611864
RN  - 0 (Blood Glucose)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 506T60A25R (Sorbitol)
RN  - C596HWF74Z 
      (1,5-anhydro-1-(5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl)-1-thioglucitol)
MH  - Adult
MH  - Aged
MH  - Asian People
MH  - Blood Glucose
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Japan
MH  - Male
MH  - Middle Aged
MH  - Single-Blind Method
MH  - Sodium-Glucose Transporter 2 Inhibitors
MH  - Sorbitol/*analogs & derivatives/pharmacokinetics/pharmacology/therapeutic use
PMC - PMC4415995
EDAT- 2015/04/10 06:00
MHDA- 2016/03/24 06:00
PMCR- 2015/04/09
CRDT- 2015/04/10 06:00
PHST- 2015/02/16 00:00 [received]
PHST- 2015/04/10 06:00 [entrez]
PHST- 2015/04/10 06:00 [pubmed]
PHST- 2016/03/24 06:00 [medline]
PHST- 2015/04/09 00:00 [pmc-release]
AID - 200 [pii]
AID - 10.1007/s12325-015-0200-x [doi]
PST - ppublish
SO  - Adv Ther. 2015 Apr;32(4):319-40. doi: 10.1007/s12325-015-0200-x. Epub 2015 Apr 9.