Drug delivery for intracerebral of flunarizine hydrochloride after intraocular administration in rats.

Abstract

Intraocular administration was a commonly route of administration in clinic, but most of the intraocular administration was only used to treat local ocular diseases. Based on the particularity of the ocular structure, this article mainly explored the feasibility of flunarizine hydrochloride in the treatment of ischemic cerebral vascular diseases (ICVD) by intraocular administration. A total of 150 SD rats were randomly divided into 3 groups with intraocular, intragastric, and intravenous administration, respectively. The doses were 14 mg/kg for intraocular and intragastric groups and 5 mg/kg for intravenous group. The plasma and brain concentration of flunarizine hydrochloride were analyzed by high performance liquid chromatography (HPLC). Main pharmacokinetic parameters and absolute bioavailability were evaluated. Brain targeting of flunarizine hydrochloride through intraocular administration was studied by drug targeting index of brain (DTIbrain). Maximum contentration (Cmax) and area under the time-concentration curve from o to t (AUC0-t) of plasma after intraocular administration were significantly higher than those of plasma after intragastric administration (both P<0.05). Cmax and AUC0-t of brain after intraocular administration were significantly higher than those of brain after intragastric administration (both P<0.05). The bioavailability of plasma and brain after intraocular administration was 18.67% and 34.67%, respectively, which was higher than 14.32% and 21.56% of plasma and brain after intragastric administration. The DTIbrain of intraocular administration was 1.84, and the DTIbrain of intragastric administration was 1.48. Flunarizine hydrochloride could be absorbed into the systemic circulation after intraocular administration. Not only the absolute bioavailability but also the brain targeting index of intraocular administration is higher than that of intragastric administration.