Phase I study on the pharmacokinetics and tolerance of ZT-1, a prodrug of huperzine A, for the treatment of Alzheimer's disease
文献类型：期刊论文
| 作者 | Jia, Jing-ying1; Zhao, Qian-hua2; Liu, Yun1; Gui, Yu-zhou3; Liu, Gang-yi1; Zhu, Da-yuan3; Yu, Chen1; Hong, Zhen2 |
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2013-07 |
| 卷号 | 34期号:7页码:976-982 |
| 关键词 | ZT-1 huperzine A prodrug AChE inhibitor drug tolerance pharmacokinetics Alzheimer's disease |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2013.7 |
| 文献子类 | Article |
| 英文摘要 | Aim: Huperzine A isolated from the Chinese herb Huperzia serrata (Thunb) Trev is a novel reversible and selective AChE inhibitor. The aim of this study was to evaluate the pharmacokinetics and tolerance of single and multiple doses of ZT-1, a novel analogue of huperzine A, in healthy Chinese subjects. Methods: This was a double-blinded, placebo-controlled, randomized, single-and multiple-dose study. For the single-dose study, 9 subjects were randomly divided into 3 groups receiving ZT-1 (0.5, 0.75 or 1 mg, po) according to a Three-way Latin Square Design. For the multiple-dose study, 9 subjects receiving ZT-1 (0.75 mg/d, po) for 8 consecutive days. In the tolerance study, 40 subjects were randomly divided into 5 groups receiving a single dose of ZT-1 (0.5, 0.75, 1, 1.25 or 1.5 mg, po). Plasma and urine concentrations of ZT-1 and Hup A were determined using LC-MS/MS. Pharmacokinetic parameters, including C-max, AUC(0-72) (h) and AUC(0-infinity) were calculated. Tolerance assessments were conducted throughout the study. Results: ZT-1 was rapidly absorbed and converted into huperzine A, thus the plasma and urine concentrations of ZT-1 were below the limit of quantification (<0.05 ng/mL). After single-dose administration of ZT-1, the mean t(max) of huperzine A was 0.76-0.82 h; the AUC(0-72 h) and C-max of huperzine A showed approximately dose-proportional increase over the dose range of 0.5-1 mg. After the multiple-dose administration of ZT-1, a steady-state level of huperzine A was achieved within 2 d. No serious adverse events were observed. Conclusion: ZT-1 is a pro-drug that is rapidly absorbed and converted into huperzine A, and ZT-1 is well tolerated in healthy Chinese volunteers. |
| WOS关键词 | CHOLINESTERASE INHIBITOR ; CHOLINERGIC HYPOTHESIS ; PROGRESS ; RAT ; MEDICINE ; VITRO ; DRUG |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:4874892 |
| WOS记录号 | WOS:000321332700014 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277557]  |
| 专题 | 天然药物化学研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Yu, Chen |
| 作者单位 | 1.Shanghai Xuhui Cent Hosp, Cent Lab, Shanghai 200031, Peoples R China; 2.Fudan Univ, Huashan Hosp, Dept Neurol, Shanghai 200031, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jia, Jing-ying,Zhao, Qian-hua,Liu, Yun,et al. Phase I study on the pharmacokinetics and tolerance of ZT-1, a prodrug of huperzine A, for the treatment of Alzheimer's disease[J]. ACTA PHARMACOLOGICA SINICA,2013,34(7):976-982. |
| APA | Jia, Jing-ying.,Zhao, Qian-hua.,Liu, Yun.,Gui, Yu-zhou.,Liu, Gang-yi.,...&Hong, Zhen.(2013).Phase I study on the pharmacokinetics and tolerance of ZT-1, a prodrug of huperzine A, for the treatment of Alzheimer's disease.ACTA PHARMACOLOGICA SINICA,34(7),976-982. |
| MLA | Jia, Jing-ying,et al."Phase I study on the pharmacokinetics and tolerance of ZT-1, a prodrug of huperzine A, for the treatment of Alzheimer's disease".ACTA PHARMACOLOGICA SINICA 34.7(2013):976-982. |
入库方式： OAI收割
来源：上海药物研究所
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