Distribution of nimodipine in brain following intranasal administration in rats.
OBJECTIVE
To determine whether nasally applied nimodipine (NM) could improve its systemic bioavailability and be transported directly from the nasal cavity to the brain.


METHODS
NM was administered nasally, intravenously (iv), and orally to male Sprague-Dawley rats. At different times post dose, blood, cerebrospinal fluid (CSF), and brain tissue samples were collected, and the concentrations of NM in the samples were analyzed by HPLC.


RESULTS
Oral systemic bioavailability of NM in rats was 1.17 %, nasal dosing improved bioavailibility to 67.4 %. Following intranasal administration, NM concentrations in olfactory bulb (OB) within 30 min post dose were found significant higher than in the other brain tissues. However, similar NM levels in different brain regions were observed after iv injection. AUC in CSF and OB from the nasal route was 1.26 and 1.39 fold compared with the iv route, respectively. The brain-to-plasma AUC ratios were significantly higher after nasal administration than after iv administration (P<0.01).


CONCLUSIONS
Nasally administered NM could markedly improve the bioavailability and a fraction of the NM dose could be transported into brain via the olfactory pathway in rats.
Zhang
Qi-zhi
QZ
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, China.
Jiang
Xin-guo
XG
Wu
Chun-hua
CH
D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D009553:Nimodipine / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D009830:Olfactory Bulb / Q000378:metabolism; D009833:Olfactory Pathways; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D002121:Calcium Channel Blockers; D009553:Nimodipine