@article{APS7940,
author = {Jing-ying Jia and Qian-hua Zhao and Yun Liu and Yu-zhou Gui and Gang-yi Liu and Da-yuan Zhu and Chen Yu and Zhen Hong},
title = {Phase I study on the pharmacokinetics and tolerance of ZT-1, a prodrug of huperzine A, for the treatment of Alzheimer's disease},
journal = {Acta Pharmacologica Sinica},
volume = {34},
number = {7},
year = {2016},
keywords = {},
abstract = {Jing-ying JIA1, #, Qian-hua ZHAO2, #, Yun LIU1, Yu-zhou GUI3, Gang-yi LIU1, Da-yuan ZHU3, Chen YU1, *, Zhen HONG2, *
1Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai 200031, China; 2Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200031, China; 3State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031, China
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 Cmax, AUC0–72 h, and AUC0–∞ 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 (},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/7940}
}