PMID- 36543754
OWN - NLM
STAT- MEDLINE
DCOM- 20230412
LR  - 20230601
IS  - 1552-4604 (Electronic)
IS  - 0091-2700 (Linking)
VI  - 63
IP  - 5
DP  - 2023 May
TI  - Evaluation of the Pharmacokinetics of Dapagliflozin in Patients With Chronic 
      Kidney Disease With or Without Type 2 Diabetes Mellitus.
PG  - 551-559
LID - 10.1002/jcph.2196 [doi]
AB  - Evidence shows that sodium-glucose cotransporter 2 inhibitors, such as 
      dapagliflozin, can delay the progressive decline of kidney function in patients 
      with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). We used a 
      population pharmacokinetics (popPK) model to characterize the pharmacokinetics of 
      dapagliflozin in patients with CKD and compare dapagliflozin systemic exposure in 
      different populations, such as CKD with or without T2DM and T2DM without CKD. A 
      2-compartmental popPK model was developed from a previous popPK model. The final 
      popPK model was based on 9715 dapagliflozin plasma concentrations from 3055 
      patients included in clinical studies involving adults with CKD with or without 
      T2DM, adults with T2DM, healthy subjects, and pediatric patients with T2DM. 
      Overall, the apparent clearance for patients treated with dapagliflozin was 
      21.6 L/h, similar to previous estimates in adults with T2DM and healthy subjects 
      (22.9 L/h). Model-derived area under the plasma concentration-time curve (AUC) 
      was not meaningfully different between patients with CKD with and without T2DM. 
      Median AUC was 1.6-fold higher in adult patients with CKD with T2DM compared with 
      adult patients with T2DM without CKD. Compared with patients with normal kidney 
      function (estimated glomerular filtration rate >/=90 mL/min/1.73 m(2) ), median AUC 
      was 2.4-fold higher in patients with CKD (with/without T2DM) with estimated 
      glomerular filtration rate 15-29 mL/min/1.73 m(2) owing to decreased renal 
      clearance of dapagliflozin. A higher AUC was observed in patients with a higher 
      age or lower body weight but was not considered clinically relevant. This popPK 
      model adequately described dapagliflozin pharmacokinetics and found that systemic 
      exposure in patients with CKD was consistent, irrespective of T2DM status.
CI  - (c) 2022, AstraZeneca Pharmaceuticals LP. The Journal of Clinical Pharmacology 
      published by Wiley Periodicals LLC on behalf of American College of Clinical 
      Pharmacology.
FAU - Penland, Robert C
AU  - Penland RC
AD  - Clinical Pharmacology & Quantitative Pharmacology, Clinical Pharmacology & Safety 
      Sciences, Biopharmaceuticals R&D, AstraZeneca, Boston, Massachusetts, USA.
FAU - Melin, Johanna
AU  - Melin J
AD  - Clinical Pharmacology & Quantitative Pharmacology, Clinical Pharmacology & Safety 
      Sciences, Biopharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
FAU - Boulton, David W
AU  - Boulton DW
AD  - Clinical Pharmacology & Quantitative Pharmacology, Clinical Pharmacology & Safety 
      Sciences, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
FAU - Tang, Weifeng
AU  - Tang W
AD  - Clinical Pharmacology & Quantitative Pharmacology, Clinical Pharmacology & Safety 
      Sciences, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230112
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 1ULL0QJ8UC (dapagliflozin)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 0 (Glucosides)
RN  - 0 (Benzhydryl Compounds)
SB  - IM
MH  - Adult
MH  - Humans
MH  - Child
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
MH  - Glucosides/pharmacology
MH  - *Renal Insufficiency, Chronic/drug therapy
MH  - Benzhydryl Compounds/pharmacokinetics
MH  - Glomerular Filtration Rate
OTO - NOTNLM
OT  - chronic kidney disease
OT  - dapagliflozin
OT  - population pharmacokinetics
OT  - sodium-glucose cotransporter 2 inhibitor
OT  - type 2 diabetes
EDAT- 2022/12/22 06:00
MHDA- 2023/04/12 06:42
CRDT- 2022/12/21 22:42
PHST- 2022/08/01 00:00 [received]
PHST- 2022/12/18 00:00 [accepted]
PHST- 2023/04/12 06:42 [medline]
PHST- 2022/12/22 06:00 [pubmed]
PHST- 2022/12/21 22:42 [entrez]
AID - 10.1002/jcph.2196 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2023 May;63(5):551-559. doi: 10.1002/jcph.2196. Epub 2023 Jan 
      12.