Pharmacokinetics of Huperzine A after transdermal and oral administration in beagle dogs

Comparison of single and multiple dose pharmacokinetics between patches and conventional tablets of Huperzine A (Hup-A) was performed in beagle dogs to evaluate the patches’ controlled drug release characteristics in vivo, a newly developed transdermal system for treatment of Alzheimer disease. Results showed that transdermal administration of Hup-A prolonged Tmax value (24 h vs. 3 h, P < 0.01), lowered Cmax value (3.4 ± 0.2 ng mL−1 vs. 9.8 ± 1.0 ng mL−1, P < 0.01), and produced a relatively constant serum concentration within 84 h after a single transdermal dose of 4 mg/20 cm2 Hup-A patches. Following application of the patches, Hup-A serum concentrations increased for approximately 12–24 h, reaching an average Cmax of 3.4 ± 0.2 ng mL−1. Thereafter, a serum concentration of at least 2.1 ng mL−1 was maintained for up to 84 h. The serum concentration was maintained within the range of 2.4–4.3 ng mL−1 during 2-week wearing period after multiple dosing, and the degree of fluctuation at the steady state of td and po administration was significantly different (0.51 vs. 1.99, P < 0.01). This study indicates that Hup-A patches exhibited good controlled-release properties in vivo, maintained a relatively constant serum concentration within 3.5 d after wearing, and are suitable for twice-weekly application.