PMID- 26510924
OWN - NLM
STAT- MEDLINE
DCOM- 20161104
LR  - 20210504
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 18
IP  - 3
DP  - 2016 Mar
TI  - Comparison of the pharmacokinetics and pharmacodynamics of dapagliflozin in 
      patients with type 1 versus type 2 diabetes mellitus.
PG  - 236-40
LID - 10.1111/dom.12594 [doi]
AB  - AIMS: To compare the pharmacokinetics and pharmacodynamics of dapagliflozin in 
      patients with type 1 diabetes mellitus (T1DM) versus type 2 diabetes mellitus 
      (T2DM) in order to explore the potential of dapagliflozin as add-on therapy to 
      insulin in patients with T1DM. METHODS: Steady-state pharmacokinetics and 
      pharmacodynamics of dapagliflozin (1-100 mg) were evaluated in a meta-analysis of 
      patients with T1DM or T2DM. A model was constructed of the relationship between 
      dapagliflozin systemic exposure and urinary glucose excretion (UGE) in patients 
      with T1DM versus those with T2DM. RESULTS: Data were analysed from 160 patients 
      (T1DM, n = 70; T2DM, n = 90). Dapagliflozin systemic exposure (maximum 
      concentration and area under the curve) increased similarly in a dose-related 
      manner in both patient populations. Dose-dependent increases in 24-h UGE were 
      observed with dapagliflozin in both populations. Unadjusted results showed that 
      with regard to UGE response, dapagliflozin was more potent in patients with T1DM 
      mean half-maximum effective concentration [EC50 ] = 2.72 ng/ml [95% confidence 
      interval (CI) 1.14, 5.08] than in patients with T2DM [EC50  = 12.2 ng/ml (95% CI 
      4.91, 21.1)]. After normalization for baseline fasting plasma glucose, estimated 
      glomerular filtration rate and UGE, however, the UGE potency of dapagliflozin was 
      similar between the two populations [T1DM: mean EC50 , 8.12 ng/ml (95% CI 2.95, 
      14.6); T2DM: mean EC50 , 7.75 ng/ml (95% CI 1.35, 18.1)]. CONCLUSIONS: 
      Dapagliflozin pharmacokinetics and the predicted UGE dose exposure response to 
      dapagliflozin were similar in patients with T1DM and those with T2DM and suggest 
      that the dapagliflozin dosages currently used for the treatment of T2DM may 
      provide benefit as add-on therapy to insulin in patients with T1DM.
CI  - (c) 2015 John Wiley & Sons Ltd.
FAU - Tang, W
AU  - Tang W
AD  - AstraZeneca, Gaithersburg, MD, USA.
FAU - Leil, T A
AU  - Leil TA
AD  - Bristol-Myers Squibb, Princeton, NJ, USA.
FAU - Johnsson, E
AU  - Johnsson E
AD  - AstraZeneca Gothenburg, Molndal, Sweden.
FAU - Boulton, D W
AU  - Boulton DW
AD  - AstraZeneca, Gaithersburg, MD, USA.
FAU - LaCreta, F
AU  - LaCreta F
AD  - Bristol-Myers Squibb, Princeton, NJ, USA.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
DEP - 20160108
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Blood Glucose)
RN  - 0 (Glucosides)
RN  - 0 (Hypoglycemic Agents)
RN  - 1ULL0QJ8UC (dapagliflozin)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Benzhydryl Compounds/*pharmacokinetics
MH  - Blood Glucose/analysis
MH  - Diabetes Mellitus, Type 1/drug therapy/*metabolism
MH  - Diabetes Mellitus, Type 2/drug therapy/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Fasting/blood
MH  - Glomerular Filtration Rate
MH  - Glucose/metabolism
MH  - Glucosides/*pharmacokinetics
MH  - Glycosuria/drug therapy/urine
MH  - Humans
MH  - Hypoglycemic Agents/*pharmacokinetics
OTO - NOTNLM
OT  - dapagliflozin
OT  - pharmacodynamics
OT  - pharmacokinetics
OT  - type 1 diabetes
OT  - type 2 diabetes
EDAT- 2015/10/30 06:00
MHDA- 2016/11/05 06:00
CRDT- 2015/10/30 06:00
PHST- 2015/07/21 00:00 [received]
PHST- 2015/10/15 00:00 [revised]
PHST- 2015/10/23 00:00 [accepted]
PHST- 2015/10/30 06:00 [entrez]
PHST- 2015/10/30 06:00 [pubmed]
PHST- 2016/11/05 06:00 [medline]
AID - 10.1111/dom.12594 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2016 Mar;18(3):236-40. doi: 10.1111/dom.12594. Epub 2016 Jan 
      8.