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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 대한약리학회 The Korean Journal of Physiology & Pharmacology The Korean Journal of Physiology & Pharmacology 제23권 제1호
- 발행연도
- 2019.1
- 수록면
- 55 - 62 (8page)
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초록· 키워드
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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 T1/2 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.
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참고문헌 (32)
참고문헌 신청
American Diabetes Association / 2010 / Diagnosis and classification of diabetes mellitus / Diabetes Care 33(Suppl 1):S62~S69
Yamagishi S / 2005 / Diabetic vascular complications : pathophysiology, biochemical basis and potential therapeutic strategy / Curr Pharm Des 11:2279~2299
Ceriello A / 2005 / Postprandial hyperglycemia and diabetes complications:is it time to treat? / Diabetes 54:1~7
Maruthur NM / 2016 / Diabetes medications as monotherapy or metformin-based combination therapy for type 2diabetes : a systematic review and meta-analysis / Ann Intern Med 164:740~751
Cefalu WT / 2007 / Pharmacotherapy for the treatment of patients with type 2 diabetes mellitus : rationale and specific agents / Clin Pharmacol Ther 81:636~649
Yamagishi S / 2005 / Diabetic vascular complications : pathophysiology, biochemical basis and potential therapeutic strategy / Curr Pharm Des 11:2279~2299
Ceriello A / 2005 / Postprandial hyperglycemia and diabetes complications:is it time to treat? / Diabetes 54:1~7
Maruthur NM / 2016 / Diabetes medications as monotherapy or metformin-based combination therapy for type 2diabetes : a systematic review and meta-analysis / Ann Intern Med 164:740~751
Cefalu WT / 2007 / Pharmacotherapy for the treatment of patients with type 2 diabetes mellitus : rationale and specific agents / Clin Pharmacol Ther 81:636~649
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