PMID- 26280756
OWN - NLM
STAT- MEDLINE
DCOM- 20160511
LR  - 20221207
IS  - 1865-8652 (Electronic)
IS  - 0741-238X (Print)
IS  - 0741-238X (Linking)
VI  - 32
IP  - 8
DP  - 2015 Aug
TI  - Pharmacokinetics, Pharmacodynamics, and Safety of Canagliflozin in Japanese 
      Patients with Type 2 Diabetes Mellitus.
PG  - 768-82
LID - 10.1007/s12325-015-0234-0 [doi]
AB  - INTRODUCTION: Canagliflozin is a sodium glucose co-transporter 2 inhibitor 
      approved worldwide for the treatment of patients with type 2 diabetes mellitus 
      (T2DM). The present study evaluated pharmacokinetics, pharmacodynamics, and 
      safety of canagliflozin in Japanese patients with T2DM. METHODS: Canagliflozin, 
      at doses of 25, 100, 200, or 400 mg, was administered as a single dose and, after 
      a washout of 1 day, in repeated doses for 14 consecutive days to 61 subjects in a 
      randomized, double-blind, placebo-controlled study. Plasma concentrations of 
      canagliflozin and urinary glucose excretion (UGE) were measured, and renal 
      threshold for glucose excretion (RTG) was calculated. Safety was evaluated on the 
      basis of adverse event (AE) reports, blood and urine laboratory parameters, and 
      vital signs. RESULTS: Plasma canagliflozin maximum concentration and area under 
      the concentration-time curve (AUC) values increased in a dose-dependent manner 
      with the time to maximum concentration (t max) of 1.0 h and elimination half-life 
      (t 1/2) of 10.22-13.26 h on Day 1. No significant changes in t max and t 1/2 were 
      observed after multiple-dose administration. The linearity factors, as calculated 
      from the ratios of AUC0-24h on Day 16 to AUC0-infinity on Day 1, were close to 1 in all 
      canagliflozin groups. Canagliflozin increased UGE0-24h (80-110 g/day with 
      canagliflozin >/=100 mg) and decreased RTG from the first day of treatment; these 
      effects were sustained during the entire period of multiple administration. No 
      significant AEs were noted. Urine volume was slightly increased on Day 1, but 
      subsequent changes after repeated doses for 14 days were small. Urinary sodium 
      tended to be higher in the early treatment period, whereas no particular change 
      was observed in serum osmolality and hematocrit. CONCLUSION: Canagliflozin 
      increased UGE, decreased RTG, and was well tolerated throughout the entire period 
      of multiple administrations in Japanese patients with T2DM. FUNDING: Mitsubishi 
      Tanabe Pharma Corporation. TRIAL REGISTRATION: ClinicalTrials.gov#NCT00707954.
FAU - Iijima, Hiroaki
AU  - Iijima H
AD  - Medical Affairs Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan. 
      Iijima.Hiroaki@mm.mt-pharma.co.jp.
FAU - Kifuji, Takayuki
AU  - Kifuji T
AD  - Development Division, Clinical Pharmacology Department, Mitsubishi Tanabe Pharma 
      Corporation, Tokyo, Japan.
FAU - Maruyama, Nobuko
AU  - Maruyama N
AD  - Development Division, Clinical Research Department II, Mitsubishi Tanabe Pharma 
      Corporation, Tokyo, Japan.
FAU - Inagaki, Nobuya
AU  - Inagaki N
AD  - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate 
      School of Medicine, Kyoto, Japan.
LA  - eng
SI  - ClinicalTrials.gov/NCT00707954
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150818
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  - 0SAC974Z85 (Canagliflozin)
MH  - Adult
MH  - Aged
MH  - Asian People
MH  - Blood Glucose/analysis
MH  - *Canagliflozin/administration & dosage/adverse effects/pharmacokinetics
MH  - Diabetes Mellitus, Type 2/blood/*drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Drug Monitoring/methods
MH  - Female
MH  - Half-Life
MH  - Humans
MH  - Hypoglycemic Agents/administration & dosage/adverse effects/pharmacokinetics
MH  - Male
MH  - Middle Aged
MH  - Sodium-Glucose Transporter 2 Inhibitors
MH  - Treatment Outcome
PMC - PMC4569680
OTO - NOTNLM
OT  - Canagliflozin
OT  - Dehydration
OT  - Japanese patients
OT  - Pharmacodynamics
OT  - Pharmacokinetics
OT  - Sodium glucose co-transporter 2 inhibitor
OT  - Type 2 diabetes mellitus
OT  - Urine volume
EDAT- 2015/08/19 06:00
MHDA- 2016/05/12 06:00
PMCR- 2015/08/18
CRDT- 2015/08/18 06:00
PHST- 2015/07/10 00:00 [received]
PHST- 2015/08/18 06:00 [entrez]
PHST- 2015/08/19 06:00 [pubmed]
PHST- 2016/05/12 06:00 [medline]
PHST- 2015/08/18 00:00 [pmc-release]
AID - 10.1007/s12325-015-0234-0 [pii]
AID - 234 [pii]
AID - 10.1007/s12325-015-0234-0 [doi]
PST - ppublish
SO  - Adv Ther. 2015 Aug;32(8):768-82. doi: 10.1007/s12325-015-0234-0. Epub 2015 Aug 
      18.