脑内药物代谢动力学研究策略及前沿技术进展  

Research strategies and frontier technology advances in intracerebral pharmacokinetics

作　　者：班玮康 杨志宏[1] BAN Wei-kang;YANG Zhi-hong(Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100193,China)

机构地区：[1]中国医学科学院北京协和医院药用植物研究所,北京100193

出　　处：《中国药理学通报》2023年第9期1607-1612,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81973744);北京市自然科学基金资助项目(No 7173267);中国医学科学院医学与健康科技创新工程(No 2022-I2M-2-001,2022-I2M-1-018)。

摘　　要：脑内药代动力学研究模式的建立,以期真实反映药物进入脑组织后的处置及作用过程,保证脑靶向药物达到有效脑内浓度的同时,也防止非脑靶向药物对神经功能的损伤,大大提高有效性和安全性。随着药代动力学领域研究策略和分析技术的迅猛发展,脑内药代动力学技术已从传统脑组织匀浆、脑脊液抽取发展到原位在体分析技术,从侵入性技术发展到非侵入性成像技术,从宏观组织水平发展到微观细胞/亚细胞水平。多种脑内药代动力学研究方法互相补充、日益完善,逐渐形成“亚细胞-细胞-组织”全方位的脑内药代动力学研究体系,为阐明药物在脑内的动态变化规律,预测药物在脑内的作用过程奠定基础。该文综述了脑内药代动力学研究策略的沿革发展,结合国内外文献报道,客观评价各种技术方法的优势与局限性,为脑组织内药物疗效作用、毒性作用预测提供参考。The establishment of the cerebral pharmacokinetic model aims to truly reflect the disposition and course of action of drugs entering brain tissues,to ensure that brain-targeted drugs reach effective intracerebral concentrations,while preventing neurological damage from non-brain-targeted drugs,and to greatly improve effectiveness and safety.With the rapid development of research strategies and analytical techniques in the field of pharmacokinetics,intracerebral pharmacokinetic techniques have evolved from traditional brain tissue homogenization and cerebrospinal fluid extraction to in situ in vivo analysis techniques,from invasive techniques to non-invasive imaging techniques,and from the macroscopic tissue level to the microscopic cellular/subcellular level.A variety of pharmacokinetic research methods in brain are complementing each other and becoming increasingly perfect,gradually forming a comprehensive“subcellular-cellular-tissue”pharmacokinetic research system in brain,laying the foundation for elucidating the dynamic changes of drugs in brain and predicting the course of action of drugs in brain.This paper reviews the evolution and development of pharmacokinetic research strategies in brain,evaluates the advantages and limitations of various techniques and methods,and provides a reference for predicting the pharmacodynamic and toxic effects of drugs in brain tissues.

关 键 词：脑内药代动力学 血脑屏障 中枢神经系统 脑微透析 质谱成像 可视化成像 

分 类 号：R322.81[医药卫生—人体解剖和组织胚胎学] R446.9[医药卫生—基础医学] R917R969.1