PMID- 36162752
OWN - NLM
STAT- MEDLINE
DCOM- 20221107
LR  - 20221107
IS  - 1879-0720 (Electronic)
IS  - 0928-0987 (Linking)
VI  - 179
DP  - 2022 Dec 1
TI  - Prediction of janagliflozin pharmacokinetics in type 2 diabetes mellitus patients 
      with liver cirrhosis or renal impairment using a physiologically based 
      pharmacokinetic model.
PG  - 106298
LID - S0928-0987(22)00183-X [pii]
LID - 10.1016/j.ejps.2022.106298 [doi]
AB  - Janagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor for type 2 
      diabetes mellitus (T2DM). The janagliflozin pharmacokinetics (PK) in T2DM 
      patients with cirrhosis or renal impairment (RI) are unknown. To predict the 
      janagliflozin PK in these patients, we constructed a physiologically based PK 
      (PBPK) model that predicted the janagliflozin PK in normal animals. The model was 
      extrapolated to healthy humans and optimized with the measured data. A PBPK model 
      for T2DM patients was developed and optimized with the measured data. Based on 
      the physiological alterations in cirrhosis or RI patients, the T2DM model was 
      applied to predict the janagliflozin PK in these patients. Results were validated 
      using fold error values. The predicted AUC values were 21,880, 24,881, 26,996, 
      and 28,419 ng/ml.h in T2DM patients with no cirrhosis, Child-Pugh-A, B, and C, 
      respectively, and those in T2DM patients with RI-mild, RI-moderate, and RI-severe 
      were 21,810, 21,840, and 22,845 ng/ml.h, respectively. Janagliflozin exposure 
      increased with increasing cirrhosis severity, whereas it remained stable 
      regardless of the RI severity. The PBPK model predicted the janagliflozin PK in 
      patients with T2DM and liver cirrhosis or RI. Dose adjustment is less critical 
      for these patients. Risk benefit assessment in janagliflozin dosing for T2DM 
      patients with liver disease is recommended.
CI  - Copyright (c) 2022. Published by Elsevier B.V.
FAU - Zhao, Hengli
AU  - Zhao H
AD  - Department of Clinical Research Center, Central Hospital Affiliated to Shandong 
      First Medical University, Jinan 250013, China.
FAU - Wei, Yilin
AU  - Wei Y
AD  - Department of Clinical Research Center, Central Hospital Affiliated to Shandong 
      First Medical University, Jinan 250013, China.
FAU - He, Kun
AU  - He K
AD  - Department of Clinical Research Center, Central Hospital Affiliated to Shandong 
      First Medical University, Jinan 250013, China.
FAU - Zhao, Xiaoyu
AU  - Zhao X
AD  - Department of Clinical Research Center, Central Hospital Affiliated to Shandong 
      First Medical University, Jinan 250013, China.
FAU - Mu, Hongli
AU  - Mu H
AD  - Department of Clinical Research Center, Central Hospital Affiliated to Shandong 
      First Medical University, Jinan 250013, China.
FAU - Wen, Qing
AU  - Wen Q
AD  - Department of Clinical Research Center, Central Hospital Affiliated to Shandong 
      First Medical University, Jinan 250013, China. Electronic address: 
      wenq0619@126.com.
LA  - eng
PT  - Journal Article
DEP - 20220923
PL  - Netherlands
TA  - Eur J Pharm Sci
JT  - European journal of pharmaceutical sciences : official journal of the European 
      Federation for Pharmaceutical Sciences
JID - 9317982
SB  - IM
MH  - Humans
MH  - *Diabetes Mellitus, Type 2/complications/drug therapy
MH  - Liver Cirrhosis/drug therapy
MH  - Area Under Curve
MH  - *Liver Diseases
MH  - Models, Biological
OTO - NOTNLM
OT  - Janagliflozin
OT  - Liver cirrhosis
OT  - PBPK model
OT  - Renal impairment
OT  - T2DM
COIS- Declaration of Competing Interest The authors declare no conflict of interest.
EDAT- 2022/09/27 06:00
MHDA- 2022/11/08 06:00
CRDT- 2022/09/26 19:37
PHST- 2022/02/21 00:00 [received]
PHST- 2022/08/18 00:00 [revised]
PHST- 2022/09/22 00:00 [accepted]
PHST- 2022/09/27 06:00 [pubmed]
PHST- 2022/11/08 06:00 [medline]
PHST- 2022/09/26 19:37 [entrez]
AID - S0928-0987(22)00183-X [pii]
AID - 10.1016/j.ejps.2022.106298 [doi]
PST - ppublish
SO  - Eur J Pharm Sci. 2022 Dec 1;179:106298. doi: 10.1016/j.ejps.2022.106298. Epub 
      2022 Sep 23.