Safety, Pharmacokinetics and Pharmacodynamics of Hetrombopag Olamine, a Novel TPO-R Agonist, in Healthy Individuals
文献类型：期刊论文
| 作者 | Zheng, Li1; Liang, Mao-zhi1; Zeng, Xiao-ling3; Li, Cai-zheng1; Zhang, Yi-fan2 ; Chen, Xiao-yan2; Zhu, Xi3; Xiang, An-bo3
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| 刊名 | BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
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| 出版日期 | 2017-11 |
| 卷号 | 121期号:5页码:414-422 |
| ISSN号 | 1742-7835 |
| DOI | 10.1111/bcpt.12815 |
| 文献子类 | Article |
| 英文摘要 | Hetrombopag olamine (hetrombopag) is a novel small-molecule, orally bioavailable, non-peptide thrombopoietin (TPO) receptor agonist that is being developed as the treatment for thrombocytopenia. Two randomized, placebo-controlled phase I studies were conducted in 72 healthy individuals to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of hetrombopag. Hetrombopag was orally administered with a single dose in five dose cohorts (5 mg, 10 mg, 20 mg, 30 mg or 40 mg) in the first study, and given once daily for 10 days in three dose cohorts (2.5 mg, 5.0 mg or 7.5 mg) in the second study, respectively. Hetrombopag was well tolerated, and the majority of adverse events associated with medicine were platelet elevations significantly above the normal range in healthy individuals. The single dose-escalation study revealed a Tmax of approximate 8 hr, and a t1/2 of 11.9 hr to 40.1 hr in a dose-prolonged manner. A dose-proportional increase in maximum concentration (Cmax) of hetrombopag was observed, with area under the curve (AUC) increasing in a greater than dose-proportional manner. The plasma concentration of hetrombopag reached the steady-state after 7 days. The steady-state AUC0-24 hr and Cmax were dose-proportionally elevated from the 5.0 mg to 7.5 mg dose level. The potent pharmacological effect of the hetrombopaginduced platelet elevation was observed in a time-and dose-dependent manner. Furthermore, the thrombopoietic response was significantly (p < 0.0001) correlated to the plasma exposure level of hetrombopag in single and multiple administration studies. Taken together, results of this study support further clinical development of hetrombopag in patients with thrombocytopenia. |
| WOS关键词 | IDIOPATHIC THROMBOCYTOPENIC PURPURA ; THROMBOPOIETIN RECEPTOR AGONIST ; CONTROLLED-TRIAL ; DOUBLE-BLIND ; OPEN-LABEL ; ELTROMBOPAG ; PLATELETS ; BIOLOGY ; MEGAKARYOCYTES ; AMG-531 |
| 资助项目 | Ministry of Science and Technology of China[2011ZX09302-001] ; Jiangsu Hengrui Medicine Co., Ltd, China[00000000] |
| WOS研究方向 | Pharmacology & Pharmacy ; Toxicology |
| 语种 | 英语 |
| WOS记录号 | WOS:000417444100006 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272415]  |
| 专题 | 上海药物代谢研究中心 |
| 通讯作者 | Zheng, Li |
| 作者单位 | 1.Sichuan Univ, West China Hosp, Inst Clin Pharmacol, Chengdu, Sichuan, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 3.Jiangsu Hengrui Med Co LTD, Dept Clin Res, Shanghai, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zheng, Li,Liang, Mao-zhi,Zeng, Xiao-ling,et al. Safety, Pharmacokinetics and Pharmacodynamics of Hetrombopag Olamine, a Novel TPO-R Agonist, in Healthy Individuals[J]. BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY,2017,121(5):414-422. |
| APA | Zheng, Li.,Liang, Mao-zhi.,Zeng, Xiao-ling.,Li, Cai-zheng.,Zhang, Yi-fan.,...&Xiang, An-bo.(2017).Safety, Pharmacokinetics and Pharmacodynamics of Hetrombopag Olamine, a Novel TPO-R Agonist, in Healthy Individuals.BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY,121(5),414-422. |
| MLA | Zheng, Li,et al."Safety, Pharmacokinetics and Pharmacodynamics of Hetrombopag Olamine, a Novel TPO-R Agonist, in Healthy Individuals".BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY 121.5(2017):414-422. |
入库方式： OAI收割
来源：上海药物研究所
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