盐酸氟桂利嗪经眼部给药后在大鼠脑内的递送

Drug delivery for intracerebral of flunarizinehydrochloride after intraocular administration in rats

目的:眼部给药是临床上常用的一种给药途径,但大多只用于治疗眼局部性疾病。基于眼部结构的特殊性,本文主要探索盐酸氟桂利嗪经眼部给药治疗缺血性脑血管疾病的可行性。方法:150只健康雄性SD大鼠随机分为滴眼组、灌胃组和注射组。滴眼组和灌胃组均以14 mg/kg的剂量给药,注射组剂量为5 mg/kg。采用高效液相色谱法(high performance liquid chromatography,HPLC)测定大鼠血浆和脑组织中的盐酸氟桂利嗪的含量,评价主要药代动力学参数和生物利用度,并通过药物脑靶向指数(drug targeting index of brain,DTIbrain)研究盐酸氟桂利嗪眼部给药的脑靶向性。结果:盐酸氟桂利嗪经眼部给药后血浆Cmax和AUC0-t,脑组织Cmax和AUC0-t均高于经灌胃给药,差异有统计学意义(均P<0.05)。经眼部给药血浆和脑组织的生物利用度分别为18.67%和34.67%,均高于经灌胃给药的14.32%和21.56%。滴眼和灌胃两种给药途径的DTIbrain分别为1.84和1.48。结论:盐酸氟桂利嗪经眼部给药后能吸收进入血液和脑组织,眼部给药的生物利用度和DTIbrain高于灌胃给药。

Objective: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.Methods: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 forintraocular and intragastric groups and 5 mg/kg for intravenous group.The plasma andbrain concentration of flunarizine hydrochloride were analyzed by high performance liquidchromatography(HPLC).Main pharmacokinetic parameters and absolute bioavailabilitywere evaluated.Brain targeting of flunarizine hydrochloride through intraocularadministration was studied by drug targeting index of brain(DTIbrain).Results:Maximum contentration(Cmax)and area under the time-concentration curve from oto t(AUC0-t)of plasma after intraocular administration were significantly higher than thoseof plasma after intragastric administration(both P<0.05).Cmax and AUC0-t of brain afterintraocular administration were significantly higher than those of brain after intragastricadministration(both P<0.05).The bioavailability of plasma and brain after intraocularadministration was 18.67%and 34.67%,respectively,which was higher than 14.32%and21.56%of plasma and brain after intragastric administration.The DTIbrain of intraocularadministration was 1.84,and the DTIbrain of intragastric administration was 1.48.Conclusion:Flunarizine hydrochloride could be absorbed into the systemic circulationafter intraocular administration.Not only the absolute bioavailability but also the braintargeting index of intraocular administration is higher than that of intragastricadministration.