Drug brain distribution following intranasal administration of Huperzine A in situ gel in rats.
OBJECTIVE
To determine the uptake extent of Huperzine A (Hup A) into the brain after intranasal administration of Hup A in situ gel to rats, and to compare the pharmacokinetic parameters between intranasal administration and iv and po.


METHODS
Hup A was administered to male Sprague-Dawley rats via nasal, iv and oral routes at the dose of 166.7, 166.7, and 500 mug/kg, respectively. Blood and brain tissue samples including the cerebrum, hippocampus, cerebellum and olfactory bulb were collected, and the concentrations of Hup A in the samples were assayed by HPLC. The area under the concentration-time curve (AUC(0-->6 h)) and the ratio of the AUC(brain) to the AUC(plasma) (drug targeting efficiency, DTE) were calculated to evaluate the brain targeting efficiency of the drug via 3 administration routes.


RESULTS
The AUC(0-->6 h) of the drug in the cerebrum, hippocampus, cerebellum, left olfactory bulb and right olfactory bulb after intranasal administration of the Hup A in situ gel were 1.5, 1.3, 1.0, 1.2, and 1.0 times of those after iv administration of the injection, and 2.7, 2.2, 1.9, 3.1, and 2.6 times of those after administration of the oral formulation. The AUC (brain0-->6 h)/AUC(plasma0-->6 h) of Hup A in the cerebrum, hippocampus and left olfactory bulb following the intranasal administration dose were significantly higher (P<0.05) than the iv dose.


CONCLUSIONS
Intranasal delivery showed a viable, non-invasive strategy for delivering the drug into brain.
Zhao
Yan
Y
Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China.
Yue
Peng
P
Tao
Tao
T
Chen
Qing-hua
QH
D000281:Administration, Intranasal; D000470:Alkaloids; D000818:Animals; D019540:Area Under Curve; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005782:Gels; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D000470:Alkaloids; D005782:Gels; D012717:Sesquiterpenes; C050426:huperzine A