| Autor: |
Min-Soo Kim, Yoo-Kyung Song, Ji-Soo Choi, Hye Young Ji, Eunsuk Yang, Joon Seok Park, Hyung Sik Kim, Min-Joo Kim, In-Kyung Cho, Suk-Jae Chung, Yoon-Jee Chae, Kyeong-Ryoon Lee |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Pharmaceutics, Vol 15, Iss 3, p 942 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1999-4923 |
| DOI: |
10.3390/pharmaceutics15030942 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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