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Biotransformation and disposition characteristics of HSK7653, a novel long-acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes

文献类型：期刊论文

作者Bian, Yi-cong4,5; Meng, Jian3; Hu, Tao4,5; Ma, Sheng4,5; Huang, Chen-rong4,5; Zhang, Feng-yi2; Wu, Qing-he2; Zhang, Hua4,5; Chen, Xiao-yan3; Miao, Li-yan1,4,5
刊名DIABETES OBESITY & METABOLISM
出版日期2024-04-22
页码9
关键词HSK7653 long-acting dipeptidyl peptidase-4 inhibitor mass balance metabolism pharmacokinetics radiolabelled
ISSN号1462-8902
DOI10.1111/dom.15605
通讯作者Zhang, Hua(zhanghua_suzhou@163.com) ; Chen, Xiao-yan(xychen@simm.ac.cn) ; Miao, Li-yan(miaoliyan@suda.edu.cn)
英文摘要Aim: To investigate the metabolism and disposition characteristics of HSK7653 in healthy male Chinese participants. Methods: A single oral dose of 80 mu Ci (25 mg) [C-14]HSK7653 capsules was administered to six healthy participants, and blood, plasma, urine and faeces were collected. Quantitative and qualitative analysis was conducted to investigate the pharmacokinetics, blood-to-plasma ratio, mass balance and metabolism of HSK7653. Results: The drug was well absorbed and reached a maximum concentration at 1.25 h. The drug-related components (HSK7653 and its metabolites) were eliminated slowly, with a half-life (t(1/2)) of 111 h. Unchanged HSK7653 contributed to more than 97% of the total radioactivity in all plasma samples. The blood-to-plasma ratio (0.573-0.845) indicated that HSK7653 did not tend to distribute into blood cells. At 504 h postdose, up to 95.9% of the dose was excreted, including 79.8% in urine and 16.1% in faeces. Most of the radioactivity (75.5% dose) in excreta was unchanged HSK7653. In addition, nine metabolites were detected in urine and faeces. The most abundant metabolite was M6-2, a dioxidation product of HSK7653, which accounted for 4.73% and 2.63% of the dose in urine and faeces, respectively. The main metabolic pathways of HSK7653 in vivo included oxidation, pyrrole ring opening and sulphonamide hydrolysation. Conclusion: HSK7653 was well absorbed, slightly metabolized and slowly excreted in humans. The high plasma exposure and long t(1/2) of HSK7653 may contribute to its long-lasting efficacy as a long-acting dipeptidyl peptidase-4 inhibitor.
WOS关键词DPP-4 INHIBITORS ; OMARIGLIPTIN ; EFFICACY
资助项目Haisco Pharmaceutical Group Co., Ltd. ; Key R&D Program of Jiangsu Province[BE2021644] ; Suzhou Health Leading Talent[GSWS2019001] ; National Clinical Research Center for Hematologic Diseases ; First Affiliated Hospital of Soochow University[2020WSC07] ; Priority Academic Program Development of the Jiangsu Higher Education Institutes (PAPD)
WOS研究方向Endocrinology & Metabolism
语种英语
WOS记录号WOS:001206483500001
出版者WILEY
源URL[http://119.78.100.183/handle/2S10ELR8/310635]  
专题中国科学院上海药物研究所
通讯作者Zhang, Hua; Chen, Xiao-yan; Miao, Li-yan
作者单位1.Soochow Univ, Affiliated Hosp 1, Natl Clin Res Ctr Hematol Dis, Suzhou, Peoples R China
2.Haisco Pharmaceut Grp Co Ltd, Chengdu, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China
4.Soochow Univ, Inst Interdisciplinary Drug Res & Translat Sci, Suzhou, Peoples R China
5.Soochow Univ, Affiliated Hosp 1, Dept Pharm, Suzhou, Peoples R China
推荐引用方式
GB/T 7714		 Bian, Yi-cong,Meng, Jian,Hu, Tao,et al. Biotransformation and disposition characteristics of HSK7653, a novel long-acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes[J]. DIABETES OBESITY & METABOLISM,2024:9.
APA Bian, Yi-cong.,Meng, Jian.,Hu, Tao.,Ma, Sheng.,Huang, Chen-rong.,...&Miao, Li-yan.(2024).Biotransformation and disposition characteristics of HSK7653, a novel long-acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes.DIABETES OBESITY & METABOLISM,9.
MLA Bian, Yi-cong,et al."Biotransformation and disposition characteristics of HSK7653, a novel long-acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes".DIABETES OBESITY & METABOLISM (2024):9.

入库方式： OAI收割

来源：上海药物研究所

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