目的 研究利培酮(risperidone, RIS)鼻用凝胶剂在大鼠体内的药动学及脑靶向性并探讨其机制。方法 采用HPLC测定RIS 在大鼠血及脑组织中的浓度;以灌胃给药作为参比,测定RIS鼻用凝胶剂经鼻腔给药后在大鼠体内的药动学和生物利用度以及在嗅球(OB)、嗅束(OT)、小脑( CL)、大脑( CR)等脑组织中的药物分布。结果 RIS分别经鼻腔与灌胃给药后,测得其药动学参数tmax分别为5和20 min, ρmax 分别为9.89与1.93 μg·mL-1,RIS鼻腔给药的相对生物利用度(Fr)为4 730%;此外,RIS鼻腔给药后在OB、OT、CL及CR等脑组织中的AUC值分别灌胃给药的45.3,10,1.5以及1.1倍。结论 RIS经鼻腔给药在体内的吸收速度明显加快,生物利用度显著提高,并具有较强脑靶向性。
Abstract
OBJECTIVE To study the pharmacokinetics of risperidone (RIS) nasal gel and its brain targeting effect and related mechanisms in rats. METHODS The concentrations of RIS in rat plasma and brain tissues were determined by HPLC method. The pharmacokinetics and relative bioavailability to oral RIS preparation of RIS nasal gel and the drug distribution in various brain tissues such as olfactory bulb (OB), olfactory tract (OT), cerebellum (CL) and cerebrum (CR) were investigated in rats. RESULTS The main pharmacokinetic parameters of RIS following nasal and oral administration such as tmax and ρmax were 5 and 20 min, 9.89 and 1.93 μg·mL-1, respectively. The relative bioavailability of nasally administered RIS was up to 4 730%. Furthermore, the AUC values of RIS nasal gel for different brain tissues such as OB, OT, CL and CR were found to be 45.3,9.9,1.5 and 1.1 folds of those of oral drug suspension, respectively. CONCLUSION The in vivo absorption rate and bioavailability of RIS following nasal administration are obviously increased and improved. Additionally, the significant brain targeting characteristics of the drug nasal gel is also confirmed.
关键词
利培酮 /
鼻用凝胶剂 /
药动学 /
生物利用度 /
脑靶向
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Key words
risperidone /
nasal gel /
pharmacokinetics /
bioavailability /
brain targeting
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中图分类号：
R944
R969
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参考文献
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脚注
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基金
内蒙古自然科学基金资助项目[2015MS(LH)0801];内蒙古医科大学科技百万工程资助项目(YKD2014KJBW012)
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