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 T(max) value (24h vs. 3h, P<0.01), lowered C(max) 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 cm(2) Hup-A patches. Following application of the patches, Hup-A serum concentrations increased for approximately 12-24h, reaching an average C(max) 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.
Ye
J C
JC
Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou, China.
Zeng
S
S
Zheng
G L
GL
Chen
G S
GS
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000470:Alkaloids; D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D004285:Dogs; D004334:Drug Administration Schedule; D005260:Female; D008297:Male; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012869:Skin Absorption; D013607:Tablets; D013997:Time Factors
D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D003692:Delayed-Action Preparations; D012717:Sesquiterpenes; D013607:Tablets; C050426:huperzine A