Drug discovery and development: A strategy of in-vivo multiple microdialysis for pharmacokinetic and neurochemical analysis


Tung-Hu Tsai, School of Medicine, National United University/National Yang-Ming University, Taipei, Taiwan (thtsai@ym.edu.tw)


Based on the drug discovery and development, this topic develops a strategy of in-vivo multiple microdialysis for pharmacokinetic and neurochemical analysis. Microdialysis coupled to liquid chromatography have been used as a biological sampling technique and continuous measurement of protein-unbound analytes from experimental animal. In-vivo multiple microdialysis is applied in the preclinical studies of absorption, distribution, metabolism and excretion for the studies of pharmacokinetics, biliary excretion, enterohepatic circulation, and neurochemical analysis. Based on the passive diffusion, microdialysis probe collect biological samples governed by the concentration gradient which allows the small molecules pass through a semi-permeable membrane. According to the clinical pharmacology, only protein-unbound form of the drug molecule can be delivered to the target sites for therapeutic actions. Our hypothesis is that the multiple microdialysis probes can be implanted to multiple targets of the experimental animal and applied to preclinical pharmacokinetic and pharmacodynamics studies. The aim of study is to develop an experimental animal model coupled to microdialysis and liquid chromatographic system for the collection microdialysates from multiple target tissues such as blood, brain, muscle, liver, kidney …etc. Several research issues, such as the regional brain distribution, the portion of drug that passes through the blood-brain barrier, liver and kidney distribution can be defined by the area under the curve (AUC) ratio of brain-to-blood (AUC brain/AUC blood), liver-to-blood (AUC liver/AUC blood) and kidney-to-blood (AUC kidney/AUC blood), respectively. Furthermore, the pros and cons of microdialysis and analytical system will be discussed in the presentation, including the detailed surgical techniques in animal experiments from rat blood, liver and kidney for the analysis of protein-unbound drug. In conclusion, in-vivo multiple microdialysis system provides feasible study strategy on the experimental animal for preclinical pharmacokinetic and pharmacodynamics studies.


Abstract Reference & Short Personal Biography of Presenting Author

Dr. Tung-Hu Tsai received Ph.D. degree from Institute of Pharmacology, National Yang-Ming University, Taiwan in 1995. He then obtained a scholarship to Department of Experimental Psychology, Neuroscience Research Center, Cambridge University, England, UK, as post-doctoral research fellow. In 1997 back to Taiwan, he served as an associate professor (1996-2002) and professor (from 2002- ) at National Yang-Ming University, Taipei Taiwan. Dr. Tsai is actively pursuing in the research for pharmaceutical medicine focus on the mechanisms of pharmacokinetic pathways, with a particular interest in bioavailability, intestinal absorption, lymphatic absorption, hepatobiliary excretion and barrier transportation, as this can be the link which connects pharmacokinetics and pharmacodynamics for drug discovery on natural products. He and his research team have published over 350 papers in peer-reviewed journals. Dr. Tsai has received an Award for excellence in teaching and research award at National Yang-Ming University. Dr. Tsai also serves on the editorial board for Journal of Pharmaceutical and Biomedical Analysis (2009- ), Biomedical Chromatography (2015- ), International Journal of Gerontology (2016- ), Journal of Chromatography B (2011- ). He was invited as an editor by Wiley publisher and published a book of Application of Microdialysis in Pharmaceutical Science, in 2011. He also serves as a Guest Editor for Molecules in 2016.


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