PMID- 19129748
OWN - NLM
STAT- MEDLINE
DCOM- 20090504
LR  - 20220409
IS  - 1532-6535 (Electronic)
IS  - 0009-9236 (Linking)
VI  - 85
IP  - 5
DP  - 2009 May
TI  - Dapagliflozin, a novel SGLT2 inhibitor, induces dose-dependent glucosuria in 
      healthy subjects.
PG  - 520-6
LID - 10.1038/clpt.2008.251 [doi]
AB  - Dapagliflozin selectively inhibits renal glucose reabsorption by inhibiting 
      sodium-glucose cotransporter-2 (SGLT2). It was developed as an 
      insulin-independent treatment approach for type 2 diabetes mellitus (T2DM). The 
      safety, tolerability, pharmacokinetics, and pharmacodynamics of the drug were 
      evaluated in single-ascending-dose (SAD; 2.5-500 mg) and multiple-ascending-dose 
      (MAD; 2.5-100 mg daily for 14 days) studies in healthy subjects. Dapagliflozin 
      exhibited dose-proportional plasma concentrations with a half-life of 
      approximately 17 h. The amount of glucosuria was also dose-dependent. Cumulative 
      amounts of glucose excreted on day 1, relating to doses from 2.5-100 mg (MAD), 
      ranged from 18 to 62 g; day 14 values were comparable to day 1 values, with no 
      apparent changes in glycemic parameters. Doses of approximately 20-50 mg provided 
      close-to-maximal SGLT2 inhibition for at least 24 h. Dapagliflozin demonstrates 
      pharmacokinetic (PK) characteristics and dose-dependent glucosuria that are 
      sustained over 24 h, which indicates that it is suitable for administration in 
      once-daily doses and suggests that further investigation of its efficacy in T2DM 
      patients is warranted.
FAU - Komoroski, B
AU  - Komoroski B
AD  - Discovery Medicine and Clinical Pharmacology, Research and Development, 
      Bristol-Myers Squibb, Princeton, New Jersey, USA.
FAU - Vachharajani, N
AU  - Vachharajani N
FAU - Boulton, D
AU  - Boulton D
FAU - Kornhauser, D
AU  - Kornhauser D
FAU - Geraldes, M
AU  - Geraldes M
FAU - Li, L
AU  - Li L
FAU - Pfister, M
AU  - Pfister M
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20090107
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Blood Glucose)
RN  - 0 (Glucosides)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (SLC5A2 protein, human)
RN  - 0 (Sodium-Glucose Transporter 2)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 1ULL0QJ8UC (dapagliflozin)
SB  - IM
MH  - Adult
MH  - Benzhydryl Compounds
MH  - Blood Glucose/drug effects
MH  - Diabetes Mellitus, Type 2/*drug therapy/physiopathology
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Glucosides/*administration & dosage/adverse effects/pharmacokinetics
MH  - Glycosuria/*chemically induced
MH  - Half-Life
MH  - Humans
MH  - Hypoglycemic Agents/*administration & dosage/adverse effects/pharmacokinetics
MH  - Male
MH  - Sodium-Glucose Transporter 2
MH  - *Sodium-Glucose Transporter 2 Inhibitors
MH  - Time Factors
EDAT- 2009/01/09 09:00
MHDA- 2009/05/05 09:00
CRDT- 2009/01/09 09:00
PHST- 2009/01/09 09:00 [entrez]
PHST- 2009/01/09 09:00 [pubmed]
PHST- 2009/05/05 09:00 [medline]
AID - clpt2008251 [pii]
AID - 10.1038/clpt.2008.251 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 2009 May;85(5):520-6. doi: 10.1038/clpt.2008.251. Epub 2009 
      Jan 7.