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Drug Research | 中国药科大学张尊建教授团队最新研究 2020-11-18

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Drug Research

Discovery, Development, Evaluation and Translational Medicine





Issue 11 · Volume 70 · November 2020


Drug Research 第11期全新上线啦!

主编为您推荐本期精选论文:以中国药科大学、药物质量与安全预警教育部重点实验室张尊建教授为通讯作者的最新研究。欢迎您免费阅读。


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Pharmacokinetics and Tissue Distribution of Loratadine, Desloratadine and Their Active Metabolites in Rat based on a Newly Developed LC-MS/MS Analytical Method

Yuxin ZhangYihua LuLijuan WangYuan TianZunjian Zhang#

Abstract //

Loratadine (LOR) and its major metabolite, desloratadine (DL) are new-generation antihistamines. The hydroxylated metabolites of them, 6-OH-DL, 5-OH-DL and 3-OH-DL are also active because of their ability to inhibit binding of pyrilamine to brain H1 receptors and a tendency for distributing to specific immune-regulatory tissues. In this study, a new validated LC-MS/MS method to simultaneously quantify LOR, DL, 6-OH-DL, 5-OH-DL and 3-OH-DL in plasma and tissues was established and applied to an investigation of their pharmacokinetics and target-tissue distribution tendency for the first time. Pharmacokinetics parameters in rat were measured and the results suggest that the body’s exposure to active metabolites were much higher than to the prodrug with LOR, but much lower with DL. The tissue distribution study shows that LOR, DL and their active metabolites were widely distributed in the liver, spleen, thymus, heart, adrenal glands and pituitary gland. For immune-regulatory tissues, the concentrations of LOR, DL and their active metabolites in the spleen were much higher than in the thymus, which is related to the spleen, one of the sites where immune responses occur. LOR and its metabolites might inhibit immune-mediated allergic inflammation through the hypothalamic-pituitary-adrenal (HPA) axis. It was also found that the concentration of LOR in the heart was highest after liver and adrenal glands while those of DL, 6-OH-DL and 5-OH-DL in the liver, adrenal glands and spleen were all higher than those in the heart, which suggests that LOR may have a greater tendency to distribute in the heart than its metabolites.

Keywords //

drug metabolism - pharmacokinetics - absorption - loratadine - desloratadine - active metabolites - tissue distribution

#张尊建 | 教授,博导 | 中国药科大学

1983年毕业于南京药学院药物分析专业,1994年博士毕业于中国药科大学药物分析专业后留校工作。先后任中国药科大学药学院副院长、药物科学研究院院长。现任药物质量与安全预警教育部重点实验室主任、药物一致性评价重点实验室主任。

主要从事药物(中药)的体内外质量分析与评价研究,近年研究多涉及药物代谢组学和药物分析毒理学。已发表学术论文240余篇,其中SCI论文150余篇。先后主持国家“重大新药创制”科技重大专项“综合性新药研发大平台-药物质量控制技术子平台(2009ZX09301-6)”、“药物一致性评价关键技术与标准研究-基于BCS分类及体内外相关性的生物豁免研究(2017ZX09101001-004)”、国家自然科学基金面上项目(81773861、81573626、81274108、30873439、30672587)、国家中医药管理局中医药科学技术研究专项(06-07ZP17)等课题10余项;主持完成了100余种不同注册分类的中西新药的质量标准、体内过程与质量评价、临床前动物及临床人体药代动力学研究。