药学学报, 2021, 56(9): 2426-2446
引用本文:
李川*, 程晨, 贾伟伟, 杨军令, 余玄, Olajide E. OLALEYE. 中药多成分药代动力学:发现与中药安全性和有效性关联的物质并揭示其药代特征[J]. 药学学报, 2021, 56(9): 2426-2446.
LI Chuan*, CHENG Chen, JIA Wei-wei, YANG Jun-ling, YU Xuan, OLALEYE Olajide E.. Multi-compound pharmacokinetic research on Chinese herbal medicines: identifying potentially therapeutic compounds and characterizing their disposition and pharmacokinetics[J]. Acta Pharmaceutica Sinica, 2021, 56(9): 2426-2446.

中药多成分药代动力学:发现与中药安全性和有效性关联的物质并揭示其药代特征
李川*, 程晨, 贾伟伟, 杨军令, 余玄, Olajide E. OLALEYE
中国科学院上海药物研究所, 新药研究国家重点实验室, 上海 201203
摘要:
中医药对中华民族健康和国家稳定发挥了重要作用,揭示决定中药有效性和安全性的物质是推进中药现代化的一项重要工作。对于化学组成复杂的中药,可通过开展多成分药代研究,根据给药后中药成分能否以某种形式被机体利用产生显著的体内暴露(以成分原形和/或代谢物形式),选拔出用于考察药效活性的中药物质,研究物质产生疗效的体内过程和药代特征,由此为揭示决定中药药效作用的物质创造条件。此外,这类多成分药代研究还可用于揭示与中药不良反应或联合用药风险关联的中药物质。经过十多年的努力,中药多成分药代研究在理论、方法、技术、应用上已取得突破,成为药代动力学的一个新分支。本文系统阐述了中药多成分药代动力学的研究方法、技术要求和分析技术,并用一类活性中药成分(三七的皂苷类成分)的研究和围绕一种已上市中药制剂(连花清瘟胶囊)的研究介绍了两类多成分药代研究实例,最后讨论了中药多成分药代研究的进一步发展。
关键词:    中药      多成分药代研究      机体利用      系统暴露      肠腔暴露      体内过程      靶标到达     
Multi-compound pharmacokinetic research on Chinese herbal medicines: identifying potentially therapeutic compounds and characterizing their disposition and pharmacokinetics
LI Chuan*, CHENG Chen, JIA Wei-wei, YANG Jun-ling, YU Xuan, OLALEYE Olajide E.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Abstract:
Chinese traditional medicine has provided, since ancient times, a basis for health care and medicine to the Chinese nation and for China's national stability. Identification of the constituents responsible for therapeutic and undesired effects of Chinese herbal medicines is a type of key research facilitating the modernization of these medicines. For a complex Chinese herbal medicine, multi-compound pharmacokinetic research is a useful approach to identifying its constituents that are bioavailable (in their unchanged and/or metabolized forms) at loci responsible for the medicine's therapeutic action and to characterizing the compounds' disposition and pharmacokinetics related to the action. In addition, such pharmacokinetic research is also useful for identifying herbal compounds associated with the medicine's adverse effects and drug-drug interaction potential. Over the past decade, great advances have been achieved in the theory, methodology, associated techniques, and their application of such multi-compound pharmacokinetic research, which has become an emerging field in pharmacokinetics. In this perspective, we elaborate on the methodology, technical requirements, and key analytical techniques of multi-compound pharmacokinetic research on Chinese herbal medicines, describe research examples regarding investigation of pharmacokinetics and disposition of a class of bioactive herbal constituents (ginsenosides of Panax notoginseng root) and pharmacokinetics-based identification of potential therapeutic compounds from a dosed Chinese herbal medicine (LianhuaQingwen capsule), and discuss follow-up development for the multi-compound pharmacokinetic research.
Key words:    Chinese herbal medicines    multi-compound pharmacokinetic research    bioavailability    systemic exposure    colon-luminal exposure    disposition    access to target of action   
收稿日期: 2021-06-08
DOI: 10.16438/j.0513-4870.2021-0839
基金项目: 国家重点研发计划项目(2018YFC1704500);国家自然科学基金资助项目(81673582).
通讯作者: 李川,Tel:86-21-50803106,E-mail:chli@simm.ac.cn
Email: chli@simm.ac.cn
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