PMID- 27299483
OWN - NLM
STAT- MEDLINE
DCOM- 20171023
LR  - 20210504
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 18
IP  - 7
DP  - 2016 Jul
TI  - Comparison of the exposure-response relationship of dapagliflozin in adult and 
      paediatric patients with type 2 diabetes mellitus.
PG  - 685-92
LID - 10.1111/dom.12647 [doi]
AB  - AIMS: To quantitatively compare the exposure-response relationship of 
      dapagliflozin in adult and paediatric patients with type 2 diabetes mellitus 
      (T2DM) and to assess the potential impact of covariate effects. METHODS: Data 
      from three clinical studies of single-dose (2.5, 5 and 10 mg), orally 
      administered dapagliflozin in adult (NCT00162305, NCT00538174) and paediatric 
      (NCT01525238) patients with T2DM were analysed to examine the relationship 
      between dapagliflozin exposure (area under concentration-time curve) and response 
      [24-h urinary glucose excretion (UGE)] using a sigmoidal maximum effect model. 
      Baseline fasting plasma glucose (FPG), estimated glomerular filtration rate 
      (eGFR), baseline 24-h UGE, sex and race were evaluated as covariates. RESULTS: 
      Data from 63 predominantly white or Asian (92.4%) adult and 20 paediatric (45.8% 
      white; 45.8% black) patients were included. The model appeared robust, with 
      predictions fitting well with observed data. Baseline eGFR, FPG and sex were 
      significant covariates in both populations; race was a significant covariate in 
      the paediatric population only. Model-predicted UGE response was higher in 
      paediatric (47.4, 67.5 and 85.9 g/24 h for 2.5, 5 and 10 mg) than in adult (31.2, 
      43.5 and 54.3 g/24 h for 2.5, 5 and 10 mg) patients, which may be associated with 
      the higher eGFR values in paediatric patients. CONCLUSIONS: After a single oral 
      dose of dapagliflozin, adult and paediatric patients with T2DM had similar 
      exposure-response relationships after accounting for significant covariates. 
      These results support the planned dosage strategy for a phase III dapagliflozin 
      safety and efficacy study in paediatric patients with T2DM, for whom treatment 
      options are currently limited.
CI  - (c) 2016 John Wiley & Sons Ltd.
FAU - Parkinson, J
AU  - Parkinson J
AD  - AstraZeneca Gothenburg, Molndal, Sweden.
FAU - Tang, W
AU  - Tang W
AD  - AstraZeneca, Gaithersburg, MD, USA.
FAU - Johansson, C-C
AU  - Johansson CC
AD  - AstraZeneca Gothenburg, Molndal, Sweden.
FAU - Boulton, D W
AU  - Boulton DW
AD  - AstraZeneca, Gaithersburg, MD, USA.
FAU - Hamren, B
AU  - Hamren B
AD  - AstraZeneca Gothenburg, Molndal, Sweden.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
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)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Area Under Curve
MH  - Benzhydryl Compounds/*administration & dosage/pharmacokinetics/pharmacology
MH  - Blood Glucose/metabolism
MH  - Child
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Female
MH  - Glucosides/*administration & dosage/pharmacokinetics/pharmacology
MH  - Humans
MH  - Hypoglycemic Agents/*administration & dosage/pharmacokinetics/pharmacology
MH  - Male
MH  - Middle Aged
MH  - Treatment Outcome
OTO - NOTNLM
OT  - covariates
OT  - dapagliflozin
OT  - exposure-response
OT  - paediatric
OT  - type 2 diabetes mellitus
EDAT- 2016/06/15 06:00
MHDA- 2017/10/24 06:00
CRDT- 2016/06/15 06:00
PHST- 2015/12/01 00:00 [received]
PHST- 2015/12/31 00:00 [revised]
PHST- 2016/02/11 00:00 [accepted]
PHST- 2016/06/15 06:00 [entrez]
PHST- 2016/06/15 06:00 [pubmed]
PHST- 2017/10/24 06:00 [medline]
AID - 10.1111/dom.12647 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2016 Jul;18(7):685-92. doi: 10.1111/dom.12647.