PMID- 36986803
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230331
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 15
IP  - 3
DP  - 2023 Mar 14
TI  - Physiologically Based Pharmacokinetic Modelling to Predict Pharmacokinetics of 
      Enavogliflozin, a Sodium-Dependent Glucose Transporter 2 Inhibitor, in Humans.
LID - 10.3390/pharmaceutics15030942 [doi]
LID - 942
AB  - Enavogliflozin is a sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor 
      approved for clinical use in South Korea. As SGLT2 inhibitors are a treatment 
      option for patients with diabetes, enavogliflozin is expected to be prescribed in 
      various populations. Physiologically based pharmacokinetic (PBPK) modelling can 
      rationally predict the concentration-time profiles under altered physiological 
      conditions. In previous studies, one of the metabolites (M1) appeared to have a 
      metabolic ratio between 0.20 and 0.25. In this study, PBPK models for 
      enavogliflozin and M1 were developed using published clinical trial data. The 
      PBPK model for enavogliflozin incorporated a non-linear urinary excretion in a 
      mechanistically arranged kidney model and a non-linear formation of M1 in the 
      liver. The PBPK model was evaluated, and the simulated pharmacokinetic 
      characteristics were in a two-fold range from those of the observations. The 
      pharmacokinetic parameters of enavogliflozin were predicted using the PBPK model 
      under pathophysiological conditions. PBPK models for enavogliflozin and M1 were 
      developed and validated, and they seemed useful for logical prediction.
FAU - Kim, Min-Soo
AU  - Kim MS
AUID- ORCID: 0000-0001-9229-4701
AD  - College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
FAU - Song, Yoo-Kyung
AU  - Song YK
AUID- ORCID: 0000-0003-0553-9892
AD  - Laboratory Animal Resource Center, Korea Research Institute of Bioscience and 
      Biotechnology, Cheongju 28116, Republic of Korea.
FAU - Choi, Ji-Soo
AU  - Choi JS
AD  - Life Science Institute, Daewoong Pharmaceutical, Yongin 17028, Republic of Korea.
AD  - School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
FAU - Ji, Hye Young
AU  - Ji HY
AD  - Life Science Institute, Daewoong Pharmaceutical, Yongin 17028, Republic of Korea.
FAU - Yang, Eunsuk
AU  - Yang E
AD  - College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
FAU - Park, Joon Seok
AU  - Park JS
AD  - Life Science Institute, Daewoong Pharmaceutical, Yongin 17028, Republic of Korea.
FAU - Kim, Hyung Sik
AU  - Kim HS
AUID- ORCID: 0000-0001-7657-3970
AD  - School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
FAU - Kim, Min-Joo
AU  - Kim MJ
AD  - Laboratory Animal Resource Center, Korea Research Institute of Bioscience and 
      Biotechnology, Cheongju 28116, Republic of Korea.
FAU - Cho, In-Kyung
AU  - Cho IK
AD  - Laboratory Animal Resource Center, Korea Research Institute of Bioscience and 
      Biotechnology, Cheongju 28116, Republic of Korea.
FAU - Chung, Suk-Jae
AU  - Chung SJ
AD  - College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
AD  - Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 
      08826, Republic of Korea.
FAU - Chae, Yoon-Jee
AU  - Chae YJ
AUID- ORCID: 0000-0003-4921-4192
AD  - College of Pharmacy, Woosuk University, Wanju-gun 55338, Republic of Korea.
FAU - Lee, Kyeong-Ryoon
AU  - Lee KR
AUID- ORCID: 0000-0003-2175-8876
AD  - Laboratory Animal Resource Center, Korea Research Institute of Bioscience and 
      Biotechnology, Cheongju 28116, Republic of Korea.
AD  - Department of Bioscience, University of Science and Technology, Daejeon 34113, 
      Republic of Korea.
LA  - eng
GR  - KGM5212221/Korea Research Institute of Bioscience and Biotechnology/
GR  - 20009774/Ministry of Trade, Industry and Energy/
GR  - 2021R1I1A3056261/National Research Foundation of Korea/
PT  - Journal Article
DEP - 20230314
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC10058973
OTO - NOTNLM
OT  - DWP16001
OT  - GCC5694A
OT  - diabetes mellitus
OT  - enavogliflozin
OT  - in vitro-in vivo extrapolation
OT  - mechanistic kidney model
OT  - pharmacokinetics
OT  - physiologically based pharmacokinetic modelling
OT  - sodium-glucose cotransporter 2 inhibitor
COIS- The authors declare no conflict of interest, but Ji-Soo Choi, Hye Young Ji and 
      Joon Seok Park were employed by Daewoong Pharmaceuticals Co. Ltd. Data were 
      acquired from clinical and/or non-clinical studies conducted or provided by 
      Daewoong Pharmaceutical Co. Ltd. The data were reanalyzed by the authors. The 
      company had no role in the data analysis or interpretation, manuscript writing, 
      or publication of the results.
EDAT- 2023/03/30 06:00
MHDA- 2023/03/30 06:01
PMCR- 2023/03/14
CRDT- 2023/03/29 02:03
PHST- 2023/02/01 00:00 [received]
PHST- 2023/03/09 00:00 [revised]
PHST- 2023/03/12 00:00 [accepted]
PHST- 2023/03/30 06:01 [medline]
PHST- 2023/03/29 02:03 [entrez]
PHST- 2023/03/30 06:00 [pubmed]
PHST- 2023/03/14 00:00 [pmc-release]
AID - pharmaceutics15030942 [pii]
AID - pharmaceutics-15-00942 [pii]
AID - 10.3390/pharmaceutics15030942 [doi]
PST - epublish
SO  - Pharmaceutics. 2023 Mar 14;15(3):942. doi: 10.3390/pharmaceutics15030942.