盐酸氟桂利嗪经眼部给药后在脑区的分布特性  

Distribution characteristics of flunarizine hydrochloride in brain regions after intraocular administration

作　　者：董捷敏 代嫚嫚 何宁 DONG Jiemin;DAI Manman;HE Ning(Shanghai Henlius Biotech,Inc.,Shanghai 200233,China;School of Pharmacy,Anhui University of Chinese Medicine)

机构地区：[1]上海复宏汉霖生物技术股份有限公司,上海200233 [2]安徽中医药大学药学院

出　　处：《山西医科大学学报》2025年第1期83-90,共8页Journal of Shanxi Medical University

基　　金：安徽省自然科学基金面上项目(2108085MH312)。

摘　　要：目的 研究盐酸氟桂利嗪经眼部给药后在大鼠嗅球、丘脑、海马、大脑皮质、小脑等脑组织中的分布特性。方法 将大鼠随机分为滴眼给药组、静脉给药组和灌胃给药组,分别于给药后30,60,90,120,180,240,360 min处死大鼠取出脑组织,分离出嗅球、丘脑、海马、大脑皮质、小脑,采用液相色谱-质谱联用仪测定不同脑区中盐酸氟桂利嗪的浓度,并计算和比较主要药物动力学参数。结果 滴眼给药组盐酸氟桂利嗪在各脑区的峰浓度(C_(max))、药时曲线下面积(AUC_(0-t))和生物利用度(F)均大于灌胃给药组。滴眼给药组药物在大鼠各脑区的达峰时间从大到小的顺序为:小脑、大脑皮质、丘脑(90 min)>嗅球(30 min)>海马(10 min),C_(max)从大到小的顺序为:海马>嗅球>丘脑>小脑>大脑皮质,AUC_(0-t)从大到小的顺序为:丘脑>嗅球>海马>大脑皮质>小脑。结论 盐酸氟桂利嗪通过眼部给药后在各脑区的分布与灌胃给药相比均呈现显著差异,眼部给药后盐酸氟桂利嗪在海马和嗅球等组织中可快速达到峰浓度,且在各脑区的药物浓度均显著高于灌胃给药途径。Objective To study the distribution characteristics of flunarizine hydrochloride in olfactory bulb,thalamus,hippocampus,cerebral cortex,cerebellum and other brain tissues of rats after intraocular administration.Methods Rats were randomly divided into eye drop administration group,intravenous administration group and intragastric administration group.All rats were killed at 30,60,90,120,180,240,360 min after administration.Then the thalamus,the olfactory bulb,the hippocampus,the cerebral cortex and the cerebellum were isolated.The concentrations of flunarizine hydrochloride in different brain regions were determined by liquid chromatography-mass spectrometry,and the main pharmacokinetic parameters were calculated and compared.Results The peak concentration(C_(max)),the area under concentration-time curve(AUC_(0-t)),and the bioavailability(F)values of flunarizine hydrochloride in all brain regions were higher in intraocular administration group than in intragastric administration group.In intraocular administration group,the time to peak was faster in hippocampus(10 min)than in olfactory bulb(30 min),followed by cerebellum,cerebral cortex,thalamus(90 min).The C_(max) value of flunarizine hydrochloride in various brain regions arranged in descending order:hippocampus,olfactory bulb,thalamus,cerebellum,and cerebral cortex.AUC_(0-t) value arranged in descending order:thalamus,olfactory bulb,hip-pocampus,cerebral cortex,and cerebellum.Conclusion The distribution of flunarizine hydrochloride in various brain regions after intraocular administration shows significant differences compared with that after intragastric administration.The concentration of flu-narizine hydrochloride rapidly peaks in hippocampus and olfactory bulb after intraocular administration,and the concentration in each brain region is significantly higher than that of intragastric administration.

关 键 词：盐酸氟桂利嗪 眼部给药 脑组织 药物动力学 海马 视神经 生物利用度 

分 类 号：R969[医药卫生—药理学]