A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TPN171H, a Novel Phosphodiesterase Type 5 Inhibitor, in Healthy Subjects

doi:10.2147/DDDT.S308610

	A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TPN171H, a Novel Phosphodiesterase Type 5 Inhibitor, in Healthy Subjects
	Qian, Hongjie 2,3; Chen, Qian 2,3; Lang, Liyu 2,3; Zou, Yang 2,3; Pu, Huahua 2,3; Xin, Liang 2,3; Song, Rong 2,3; Li, Tingting 2,3; Zhu, Huijuan 2,3; Wang, Yu 4
刊名	DRUG DESIGN DEVELOPMENT AND THERAPY
	2021
卷号	15 页码:2947-2959
关键词	TPN171H PDE5 inhibitor safety pharmacokinetics food effect healthy subjects
ISSN号	1177-8881
DOI	10.2147/DDDT.S308610
通讯作者	Wang, Zhen(wangzhen@simm.ac.cn) ; Jia, Jingying(jyjia@shxh-centerlab.com)
英文摘要	Purpose: TPN171H is a novel, potent and selective phosphodiesterase type 5 (PDE5) inhibitor for the treatment of pulmonary arterial hypertension (PAH). The objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of TPN171H in healthy subjects after single and multiple dosing, in addition, to investigate the food effect on pharmacokinetics and safety of TPN171H. Methods: The entire study was comprised of three parts: Part I (single ascending-dose study), Part II (food effect study), and Part III (multiple ascending-dose study). A total of 63 healthy subjects were enrolled in the study. TPN171H tablet or placebo was administered per protocol requirements. Blood samples were collected at the designated time points for pharmacokinetic analysis. Safety was assessed by clinical examinations and adverse events. Results: In Part I, AUC and C-max were proved to be linear within the 5-30 mg dose range. T1/2 of TPN171H was 8.02-10.88 h. In Part II, we figured out that TPN171H administration under fed condition could decrease C-max, prolong T-max, but had no effect on AUC. In Part III, the accumulation ratio at steady- state for AUC and C-max indicated that TPN171H has a slight accumulation upon repeated dosing. Subjects were generally tolerable after TPN171H administration. Compared with other PDE5 inhibitors, TPN171H was found to have no impact on blood pressure and color discrimination. Conclusion: TPN171H was safe and generally tolerated in healthy subjects. Based on the half-life, food effect, and safety profile of TPN171H, we recommend a once-daily, post-meal administration of TPN171H in subsequent clinical studies in healthy subjects and patients with PAH.
资助项目	Vigonvita Life Science Co., Ltd. ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002] ; Strategic Priority Research Program of Chinese Academy of Sciences[XDA12040103]
WOS关键词	HUMAN PULMONARY-ARTERY ; SILDENAFIL CITRATE ; MECHANISMS ; THERAPY ; DISEASE
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	DOVE MEDICAL PRESS LTD
WOS记录号	WOS:000670287800005
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/296884]
专题	中国科学院上海药物研究所
通讯作者	Wang, Zhen; Jia, Jingying
作者单位	1.Vigonvita Life Sci Co Ltd, Suzhou 215123, Peoples R China 2.Shanghai Xuhui Cent Hosp, Cent Lab, Shanghai 200031, Peoples R China 3.Shanghai Engn Res Ctr Phase I Clin Res & Qual Con, Shanghai 200031, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Qian, Hongjie,Chen, Qian,Lang, Liyu,et al. A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TPN171H, a Novel Phosphodiesterase Type 5 Inhibitor, in Healthy Subjects[J]. DRUG DESIGN DEVELOPMENT AND THERAPY,2021,15:2947-2959.
APA	Qian, Hongjie.,Chen, Qian.,Lang, Liyu.,Zou, Yang.,Pu, Huahua.,...&Jia, Jingying.(2021).A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TPN171H, a Novel Phosphodiesterase Type 5 Inhibitor, in Healthy Subjects.DRUG DESIGN DEVELOPMENT AND THERAPY,15,2947-2959.
MLA	Qian, Hongjie,et al."A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TPN171H, a Novel Phosphodiesterase Type 5 Inhibitor, in Healthy Subjects".DRUG DESIGN DEVELOPMENT AND THERAPY 15(2021):2947-2959.