Effects of Food on the Pharmacokinetic Properties and Mass Balance of Henagliflozin in Healthy Male Volunteers

doi:10.1016/j.clinthera.2021.07.008

	Effects of Food on the Pharmacokinetic Properties and Mass Balance of Henagliflozin in Healthy Male Volunteers
	Chen, Zhen-dong 1; Chen, Qian 2,3; Zhu, Yun-ting 1; Zhang, Yi-fan 1; Zhan, Yan 1; Chen, Xiao-fei 2,3; Liang, Xin 2,3; Jia, Jing-ying 2,3; Yu, Chen 2,3; Liu, Hai-yan 4
刊名	CLINICAL THERAPEUTICS
	2021-09-01
卷号	43 期号:9 页码:E264-E273
关键词	henagliflozin food effects mass balance pharmacokinetics SGLT-2 inhibitor
ISSN号	0149-2918
DOI	10.1016/j.clinthera.2021.07.008
通讯作者	Liu, Yan-mei() ; Zhong, Da-fang(ymliu@shxh-centerlab.com)
英文摘要	Purpose: Henagliflozin is a highly selective and effective sodium glucose co-transporter (SGLT)-2 inhibitor developed for the treatment of patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the effects of meal intake on the pharmacokinetic properties of henagliflozin, and to understand the excretion pathways of henagliflozin in humans. Methods: In this Phase I, randomized, open-label, single-dose, two-period crossover study, 12 healthy male Chinese volunteers were randomized to receive either henagliflozin 10 mg in the fasted condition followed by henagliflozin 10 mg in the fed condition, or the reverse schedule, with the two administrations separated by a washout period of at least 7 days. Samples of blood, urine, and feces were collected and analyzed for the investigation of the pharmacokinetic profile and excretion pathways in the fasted and fed conditions. Any adverse events that occurred throughout the study were recorded for tolerability assessment. Findings: After the administration of a single oral dose of henagliflozin, mean (SD) plasma AUC(0-infinity) and C-max were 1200 (274) h middot ng/mL and 179 (48.8) ng/mL, respectively, in the fasted state and were decreased to 971 (245) h middot ng/mL and 115 (34.2) ng/mL in the fed state. The fed/fasted ratios (90% CIs) of the geometric mean values of C-max, AUC(0-t), and AUC(0-infinity) were 64% (54%-76%), 80% (76%-85%), and 80% (76%-85%), respectively. The median (range) Tmax was prolonged from 1.5 (1-3) hours in the fasted condition to 2 (1.5-6) hours in the fed condition. Mass-balance testing revealed that henagliflozin was eliminated primarily as the parent drug in feces and as glucuronide metabolites in urine. In the fasted state, the cumulative excretion percentages of the parent drug and its metabolites to dose in feces and urine were 40.6% and 33.9%, respectively. The values in the fed condition were changed to 50.4% and 25.5%, respectively. These findings suggest that postprandial administration decreases the absorption rate and the extent of henagliflozin exposure in humans, but has no effect on the metabolism or elimination of the drug. (C) 2021 Elsevier Inc.
资助项目	Jiangsu Hengrui Pharmaceuticals Company Ltd
WOS关键词	GLUCOSE COTRANSPORTER 2 ; PHARMACODYNAMIC PROFILES ; INHIBITOR ; DAPAGLIFLOZIN
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER
WOS记录号	WOS:000718006700002
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/299024]
专题	中国科学院上海药物研究所
通讯作者	Liu, Yan-mei; Zhong, Da-fang
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China 2.Shanghai Xuhui Cent Hosp, Shanghai, Peoples R China 3.Shanghai Engn Res Ctr Phase I Clin Res & Qual Con, Shanghai, Peoples R China 4.Jiangsu Hengrui Pharmaceut Co Ltd, Lianyungang, Peoples R China
推荐引用方式 GB/T 7714	Chen, Zhen-dong,Chen, Qian,Zhu, Yun-ting,et al. Effects of Food on the Pharmacokinetic Properties and Mass Balance of Henagliflozin in Healthy Male Volunteers[J]. CLINICAL THERAPEUTICS,2021,43(9):E264-E273.
APA	Chen, Zhen-dong.,Chen, Qian.,Zhu, Yun-ting.,Zhang, Yi-fan.,Zhan, Yan.,...&Zhong, Da-fang.(2021).Effects of Food on the Pharmacokinetic Properties and Mass Balance of Henagliflozin in Healthy Male Volunteers.CLINICAL THERAPEUTICS,43(9),E264-E273.
MLA	Chen, Zhen-dong,et al."Effects of Food on the Pharmacokinetic Properties and Mass Balance of Henagliflozin in Healthy Male Volunteers".CLINICAL THERAPEUTICS 43.9(2021):E264-E273.