Pharmacological evaluation of HM41322, a novel SGLT1/2 dual inhibitor, in vitro and in vivo.
10.4196/kjpp.2019.23.1.55
- Author:
Kyu Hang LEE
1
;
Sang Don LEE
;
Namdu KIM
;
Kwee Hyun SUH
;
Young Hoon KIM
;
Sang Soo SIM
Author Information
1. Hanmi Research Center, Hanmi Pharmaceutical Co., Ltd, Hwaseong 18469, Korea.
- Publication Type:Original Article
- Keywords:
Dapagliflozin;
Diabetes mellitus;
HM41322;
SGLT1/2 dual inhibitor
- MeSH:
Animals;
Diabetes Mellitus;
Glucose;
In Vitro Techniques*;
Kidney;
Mice;
Plasma
- From:The Korean Journal of Physiology and Pharmacology
2019;23(1):55-62
- CountryRepublic of Korea
- Language:English
-
Abstract:
HM41322 is a novel oral sodium-glucose cotransporter (SGLT) 1/2 dual inhibitor. In this study, the in vitro and in vivo pharmacokinetic and pharmacologic profiles of HM41322 were compared to those of dapagliflozin. HM41322 showed a 10-fold selectivity for SGLT2 over SGLT1. HM41322 showed an inhibitory effect on SGLT2 similar to dapagliflozin, but showed a more potent inhibitory effect on SGLT1 than dapagliflozin. The maximum plasma HM41322 level after single oral doses at 0.1, 1, and 3 mg/kg were 142, 439, and 1830 ng/ml, respectively, and the T(1/2) was 3.1 h. HM41322 was rapidly absorbed and reached the circulation within 15 min. HM41322 maximized urinary glucose excretion by inhibiting both SGLT1 and SGLT2 in the kidney. HM41322 3 mg/kg caused the maximum urinary glucose excretion in normoglycemic mice (19.32±1.16 mg/g) at 24 h. In normal and diabetic mice, HM41322 significantly reduced glucose excursion. Four-week administration of HM41322 in db/db mice reduced HbA1c in a dose dependent manner. Taken together, HM41322 showed a favorable preclinical profile of postprandial glucose control through dual inhibitory activities against SGLT1 and SGLT2.
