Modulation of brain delivery and copulation by intranasal apomorphine hydrochloride

Clinical studies showed apomorphine (APO) nasal spray was well tolerated, with lower dose and less side effect in treatment of erectile dysfunction compared with its sublingual formulation. The aim of this paper was to find out whether there exists any direct drug transport from nasal cavity to brain following intranasal administration to rats. Pharmacokinetic results illustrated there were no significant differences of AUC0→120 values in most brain regions and cerebrospinal fluid (CSF) through intranasal delivery route compared with subcutaneous injection, while its plasma AUC0→120 was only one-half. APO brain and CSF profiles after intranasal administration displayed faster onset compared with subcutaneous delivery. About 35–50% of APO content at 2 h, by calculating brain drug direct transport percentage, were transported to different brain regions via the olfactory pathway. In addition, the similar brain drug concentration–time profiles through intranasal delivery compared with subcutaneous route had good correlation with its equivalent sexual stimulant activity on copulatory behaviour in rats. Therefore, we could conclude a nose-to-brain pathway for APO intranasal delivery, which significantly increased brain accumulation of APO. Current experiments also explained the reason why the intranasal application of APO could be an effective alternative to subcutaneous and oral formulations.