Abstract
The pharmacokinetics of huperzine A in dogs after single intravenous and oral administrations was investigated. Concentrations of huperzine A were determined by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Pharmacokinetic parameters were calculated by non-compartmental methods. After single intravenous administration, the Cmax, T1/2, AUC0-t, AUC0-∞, CL, Vd and Vss were 5.55 ± 1.61 μg/L, 5.02 ± 0.31 h, 16.04 ± 5.24, 16.49 ± 5.29 μg·h/L, 0.66 ± 0.19 L/h/kg, 4.76 ± 1.46, and 3.93 ± 1.54 L/kg, respectively. After single oral administration, the Cmax, Tmax, T1/2, AUC0-t, AUC0-∞ and oral bioavailability were 2.60 ± 0.60 μg/L, 1.25 ± 0.50 h, 5.71 ± 2.25 h, 12.90 ± 3.19, 13.78 ± 3.24 μg·h/L, and 94.4 ± 36.5 %, respectively. In conclusion, huperzine A had a rapid and nearly complete oral absorption and was extensively distributed into tissues after drug administration in dogs.
Key words
Lycopodiaceae -
Huperzia serrata
- lycopodium alkaloid - huperzine A - pharmacokinetics - bioavailability
References
-
1
Tang X C, Han Y F.
Pharmacological profile of huperzine A, a novel acetylcholinesterase inhibitor from Chinese herb.
CNS Drug Rev.
1999;
5
281-300
-
2
Zhu X Z, Li X Y, Liu J.
Recent pharmacological studies on natural products in China.
Eur J Pharmacol.
2004;
500
221-30
-
3
Xiao X Q, Yang J W, Tang X C.
Huperzine A protects rat pheochromocytoma cells against hydrogen peroxide-induced injury.
Neurosci Lett.
1999;
275
73-6
-
4
Xiao X Q, Zhang H Y, Tang X C.
Huperzine A attenuates amyloid beta-peptide fragment 25 - 35-induced apoptosis in rat cortical neurons via inhibiting reactive oxygen species formation and caspase-3 activation.
J Neurosci Res.
2002;
67
30-6
-
5
Zhou J, Tang X C.
Huperzine A attenuates apoptosis and mitochondria-dependent caspase-3 in rat cortical neurons.
FEBS Lett.
2002;
526
21-5
-
6
Zhang H Y, Tang X C.
Huperzine A attenuates the neurotoxic effect of staurosporine in primary rat cortical neurons.
Neurosci Lett.
2003;
340
91-4
-
7
Zhao H W, Li X Y.
Ginkgolide A, B and huperzine A inhibit nitric oxide-induced neurotoxicity.
Int Immunopharmacol.
2002;
2
1551-6
-
8
Wang R, Zhang H Y, Tang X C.
Huperzine A attenuates cognitive dysfunction and neuronal degeneration caused by beta-amyloid protein-(1 - 40) in rat.
Eur J Pharmacol.
2001;
421
149-56
-
9
Zhang Z, Wang X, Chen Q, Shu L, Wang J, Shan G.
Clinical efficacy and safety of huperzine A in treatment of mild to moderate Alzheimer disease, a placebo-controlled, double-blind randomized trial.
Natl Med J China.
2002;
82
941-4
-
10
Ma X C, Xin J, Wang H X, Zhang T, Tu Z H.
Acute effects of huperzine A and tacrine on rat liver.
Acta Pharmacol Sin.
2003;
24
247-50
-
11
Xu S S, Guo Z X, Wang Z, Du Z M, Xu W A, Yang J S. et al .
Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer’s disease.
Acta Pharmacol Sin.
1995;
16
391-5
-
12
Xu S S, Xie H B, Du Z M, Tong Z H, Shi Q C, Lu K M. et al .
Efficacy of tablet huperzine-A on memory and cognition in patients with benign senescent forgetfulness.
Chin J Clin Pharmacol Ther.
1997;
2
1-4
-
13
Xu S S, Cai Z Y, Qu Z W, Yang R M, Cai Y L, Wang G Q. et al .
Huperzine A in capsules and tablets for treating patients with Alzheimer’s disease.
Acta Pharmacol Sin.
1999;
20
486-90
-
14
Wang Y E, Feng J, Liu W H, Tang X C.
Pharmacokinetics of huperzine A in rats and mice.
Acta Pharmacol Sin.
1988;
9
193-6
-
15
Qian B C, Wang M, Zhou Z F, Chen K, Zhou R R, Chen G S.
Pharmacokinetics of tablet huperzine A in six volunteers.
Acta Pharmacol Sin.
1995;
16
396-8
-
16
Ye J C, Zeng S, Zhang W G, Chen G S.
Ion-pair reverse-phase high performance liquid chromatography method for determination of huperzine A in beagle dog serum.
J Chromatogr B Analyt Technol Biomed Life Sci.
2005;
817
187-91
-
17
Zhao Z G.
Huperzine A tablets.
Chin J New Drugs.
1998;
7
193-4
-
18
Wang Y W, Chu D F, Gu J K, Fawcett J P, Wu Y, Liu W H.
Liquid chromatographic-tandem mass spectrometric method for the quantitation of huperzine A in dog plasma.
J Chromatogr B Analyt Technol Biomed Life Sci.
2004;
803
375-8
Prof. Dr. Ke Liu
School of Pharmacy
Yantai University
No 32 Qingquan Road
Laishan District
Yantai
Shandong 264005
People’s Republic of China
Phone: +86-535-671-3858
Email: liuke@luye-pharm.com
