盐酸文拉法辛鼻喷剂在大鼠脑组织内药动学及脑靶向性研究  

Cerebral pharmacokinetics of venlafaxine hydrochloride nasal spray and its brain targeting in rats

作　　者：李爽 樊慧敏 丛志新 王毅[1] 吴春芝[1] 谷福根[1] LI Shuang;FAN Hui-min;CONG Zhi-xin;WANG Yi;WU Chun-zhi;GU Fu-gen(Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010050;School of Pharmacy,Inner Mongolia Medical University,Hohhot 010110)

机构地区：[1]内蒙古医科大学附属医院,呼和浩特010050 [2]内蒙古医科大学药学院,呼和浩特010110

出　　处：《中南药学》2020年第3期369-372,共4页Central South Pharmacy

基　　金：内蒙古卫生计生委资助项目(No.201701057)。

摘　　要：目的研究盐酸文拉法辛(Ven)鼻喷剂在大鼠脑组织内的药动学并评价其脑靶向性。方法采用HPLC-荧光法测定大鼠脑组织中Ven浓度;以Ven溶液灌胃给药作为参比,测定该药物鼻喷剂经鼻腔给药后,在嗅球(OB)、嗅束(OT)、大脑(CR)及小脑(CL)等不同脑组织中的药物分布并估算tmax、Cmax、AUC0~t以及相对生物利用度(Fr)等主要药动学参数。结果Ven鼻喷剂鼻腔给药后,测得药物在大鼠OB、OT、CR及CL等脑组织的tmax值均远小于灌胃给药,而Cmax与AUC0~t值均显著大于灌胃给药,两种给药途径比较,差异有统计学意义(P<0.01)。鼻腔给药Ven在OB、OT、CR及CL中的相对生物利用度分别为350.9%、331.1%、304.4%以及302.1%。结论Ven鼻喷剂药物入脑速度快、生物利用度高、脑靶向性强,是一种理想的非口服给药新剂型。Objective To investigate the pharmacokinetics of venlafaxine hydrochloride(Ven) nasal spray in the cerebral tissues of rats and further evaluate its brain targeting behaviors. Methods The concentration of Ven in the brain tissues was determined by HPLC-fluorescent method. The distribution of Ven in different brain tissues such as the olfactory bulb(OB), olfactory tract(OT), cerebrum(CR) and cerebellum(CL) after the administration of the nasal spray to rats was determined. The main pharmacokinetic parameters of Ven such as tmax, Cmax, AUC0 ~ t in OB, OT, CR and CL and the relative bioavailability(Fr) were estimated with intragastric dosing(ig) of the drug solution as reference. Results The tmax of Ven nasal spray for different brain tissues such as OB, OT, CR and CL was all less than that for ig administration of the drug solution. However, Cmax and AUC0 ~ t values of the nasal spray for the above brain tissues were all greater than those for the ig route. There was significant difference between the two dosing routes(P < 0.01). The relative bioavailability(Fr) of Ven in OB, OT, CR and CL for the drug nasal spray was 350.9%, 331.1%, 304.4% and 302.1%, respectively. Conclusion The nasal spray may be an ideal non-oral new dosage form of Ven with advantages such as rapid transport into the brain, high brain bioavailability and remarkable brain targeting.

关 键 词：盐酸文拉法辛 鼻喷剂 脑组织 药动学 脑靶向 

分 类 号：R94[医药卫生—药剂学] R96[医药卫生—药学]