PMID- 33205593
OWN - NLM
STAT- MEDLINE
DCOM- 20220127
LR  - 20221207
IS  - 2160-7648 (Electronic)
IS  - 2160-763X (Print)
IS  - 2160-763X (Linking)
VI  - 10
IP  - 7
DP  - 2021 Jul
TI  - Population Pharmacokinetic Model for Ertugliflozin in Healthy Subjects and 
      Patients With Type 2 Diabetes Mellitus.
PG  - 696-706
LID - 10.1002/cpdd.885 [doi]
AB  - Ertugliflozin is a selective sodium-glucose cotransporter 2 inhibitor approved as 
      an adjunct to diet and exercise to improve glycemic control in adults with type 2 
      diabetes mellitus (T2DM). A population pharmacokinetic (popPK) model was 
      developed to characterize the pharmacokinetics (PK) of ertugliflozin and quantify 
      the influence of intrinsic (eg, body weight, age, sex, race, estimated glomerular 
      filtration rate [eGFR], T2DM) and extrinsic (eg, food) covariates on the PK 
      parameters of ertugliflozin. The analysis was conducted using data from 15 
      clinical studies (phases 1-3) enrolling healthy subjects and patients with T2DM, 
      which included 13,691 PK observations from 2276 subjects and was performed using 
      nonlinear mixed-effects modeling. A 2-compartment popPK model with first-order 
      absorption and a lag time and first-order elimination, described the plasma 
      concentration-time profile of ertugliflozin after single and multiple dosing in 
      healthy subjects and in patients with T2DM. Apparent clearance increased with 
      increasing body weight and eGFR, was slightly lower in patients with T2DM and 
      females, and was slightly higher in Asians. Apparent central volume of 
      distribution increased with increasing body weight and was higher in females and 
      Asians. Administration of ertugliflozin with food decreased the absorption rate 
      constant (k(a) ) and relative bioavailability (F1) compared with fasted. When 
      ertugliflozin was administered without regard to food, estimates of k(a) and F1 
      were similar to those for administration with food. The popPK model successfully 
      characterized ertugliflozin exposure in healthy subjects and patients with T2DM. 
      None of the covariates evaluated had a clinically relevant effect on 
      ertugliflozin PK.
CI  - (c) 2020 Pfizer Inc. Meck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. 
      Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on 
      behalf of American College of Clinical Pharmacology.
FAU - Fediuk, Daryl J
AU  - Fediuk DJ
AD  - Pfizer Inc., Groton, Connecticut, USA.
FAU - Zhou, Susan
AU  - Zhou S
AD  - Merck & Co., Inc., Kenilworth, New Jersey, USA.
FAU - Dawra, Vikas Kumar
AU  - Dawra VK
AD  - Pfizer Inc., Groton, Connecticut, USA.
FAU - Sahasrabudhe, Vaishali
AU  - Sahasrabudhe V
AD  - Pfizer Inc., Groton, Connecticut, USA.
FAU - Sweeney, Kevin
AU  - Sweeney K
AD  - Pfizer Inc., Groton, Connecticut, USA.
LA  - eng
GR  - NCT00989079/ClinicalTrials.gov identifier/
GR  - NCT01127308/ClinicalTrials.gov identifier/
GR  - NCT01054300/ClinicalTrials.gov identifier/
GR  - NCT01223339/ClinicalTrials.gov identifier/
GR  - NCT01948986/ClinicalTrials.gov identifier/
GR  - NCT01096667/ClinicalTrials.gov identifier/
GR  - NCT01059825/ClinicalTrials.gov identifier/
GR  - NCT01986855/ClinicalTrials.gov identifier/
GR  - NCT02033889/ClinicalTrials.gov identifier/
GR  - NCT02099110/ClinicalTrials.gov identifier/
GR  - NCT01958671/ClinicalTrials.gov identifier/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201117
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
RN  - 0 (Bridged Bicyclo Compounds, Heterocyclic)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 6C282481IP (ertugliflozin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Asian People
MH  - Biological Availability
MH  - Bridged Bicyclo Compounds, Heterocyclic/*administration & dosage/pharmacokinetics
MH  - Case-Control Studies
MH  - Clinical Trials, Phase I as Topic
MH  - Clinical Trials, Phase II as Topic
MH  - Clinical Trials, Phase III as Topic
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Female
MH  - Glomerular Filtration Rate
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Models, Biological
MH  - Sodium-Glucose Transporter 2 Inhibitors/*administration & dosage/pharmacokinetics
MH  - Tissue Distribution
MH  - Young Adult
PMC - PMC8359437
OTO - NOTNLM
OT  - diabetes
OT  - ertugliflozin
OT  - population pharmacokinetics
OT  - sodium-glucose cotransporter 2 inhibitor
COIS- D.J.F., V.K.D., V.S., and K.S. are employees of Pfizer Inc., New York, NY, USA, 
      and may own shares/stock options in Pfizer Inc. S.Z. is an employee of Merck 
      Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and 
      may own stock in Merck & Co., Inc., Kenilworth, NJ, USA.
EDAT- 2020/11/19 06:00
MHDA- 2022/01/28 06:00
PMCR- 2021/08/12
CRDT- 2020/11/18 06:06
PHST- 2020/08/03 00:00 [received]
PHST- 2020/10/12 00:00 [accepted]
PHST- 2020/11/19 06:00 [pubmed]
PHST- 2022/01/28 06:00 [medline]
PHST- 2020/11/18 06:06 [entrez]
PHST- 2021/08/12 00:00 [pmc-release]
AID - CPDD885 [pii]
AID - 10.1002/cpdd.885 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2021 Jul;10(7):696-706. doi: 10.1002/cpdd.885. Epub 2020 
      Nov 17.