Phase I study on the pharmacokinetics and tolerance of ZT-1, a prodrug of huperzine A, for the treatment of Alzheimer's disease

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 subject...

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Bibliographic Details
Published in:Acta pharmacologica Sinica 2013-07, Vol.34 (7), p.976-982
Main Authors: Jia, Jing-ying, Zhao, Qian-hua, Liu, Yun, Gui, Yu-zhou, Liu, Gang-yi, Zhu, Da-yuan, Yu, Chen, Hong, Zhen
Format: Article
Language:English
Subjects:
Alkaloids - administration & dosage
Alkaloids - adverse effects
Alkaloids - pharmacokinetics
Alzheimer Disease - drug therapy
Alzheimer Disease - metabolism
Biomedical and Life Sciences
Biomedicine
Cholinesterase Inhibitors - administration & dosage
Cholinesterase Inhibitors - adverse effects
Cholinesterase Inhibitors - pharmacokinetics
Cross-Over Studies
Double-Blind Method
Humans
Huperzia
Immunology
Internal Medicine
Male
Medical Microbiology
Original
original-article
Pharmacology/Toxicology
Prodrugs - administration & dosage
Prodrugs - adverse effects
Prodrugs - pharmacokinetics
Sesquiterpenes - administration & dosage
Sesquiterpenes - adverse effects
Sesquiterpenes - pharmacokinetics
Treatment Outcome
Vaccine
Young Adult
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Summary: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–∞ 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:1671-4083
1745-7254
DOI:10.1038/aps.2013.7