Pharmacological evaluation of HM41322, a novel SGLT1/2 dual inhibitor, in vitro and in vivo
The Korean Journal of Physiology and Pharmacology
;
: 55-62, 2019.
Article
in English
| WPRIM
| ID: wpr-728025
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Plasma
/
In Vitro Techniques
/
Diabetes Mellitus
/
Glucose
/
Kidney
Limits:
Animals
Language:
English
Journal:
The Korean Journal of Physiology and Pharmacology
Year:
2019
Type:
Article
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