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Phase I study on the pharmacokinetics and tolerance of ZT-1, a prodrug of huperzine A, for the treatment of Alzheimer's disease.
- Source :
- Acta Pharmacologica Sinica; Jul2013, Vol. 34 Issue 7, p976-982, 7p, 6 Charts, 2 Graphs
- Publication Year :
- 2013
-
Abstract
- 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<subscript>max</subscript>, AUC<subscript>0-72 h</subscript> and AUC<subscript>0-∞</subscript> 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<subscript>max</subscript> of huperzine A was 0.76-0.82 h; the AUC<subscript>0-72 h</subscript> and C<subscript>max</subscript> 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 16714083
- Volume :
- 34
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Acta Pharmacologica Sinica
- Publication Type :
- Academic Journal
- Accession number :
- 88899230
- Full Text :
- https://doi.org/10.1038/aps.2013.7