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A microsensing system for the <i>in vivo</i> real-time monitoring of local drug kinetics

MetadataDetails
Publication Date2018-01-01
JournalProceedings for Annual Meeting of The Japanese Pharmacological Society
AuthorsGenki Ogata, Kai Asai, Yamato Sano, Madoka Takai, Hiroyuki Kusuhara
InstitutionsKeio University, The University of Tokyo

It is crucial to continuously measure local concentrations of systemically administered drugs in vivo in different organs and tissues. However, conventional methods require considerable samples quantities and have poor sampling rates. Additionally, they cannot address how drug kinetics correlates with target function over time. In this study, we developed a system with two different sensors. One is a needle-type of boron-doped diamond microsensor with tip diameter ļ½ž40 µm. This sensor can detect change of drug concentrations with time resolution of ļ½ž5 seconds. The other is a glass microelectrode for monitoring cellular electrophysiological responses. We first tested the bumetanide, a blocker for Na+,K+,2Cl—cotransporter blocker. This diuretic can induce deafness. In the guinea-pig cochlea injected intravenously with bumetanide, the changes of the drug concentration and the extracellular potential underlying hearing were simultaneously measured in real time. We further examined an antiepileptic drug lamotrigine, which inhibits Na+ channel, in the rat brain, and tracked its kinetics and at the same time the local field potentials mirroring neuronal activity. The action of the anticancer reagent doxorubicin was also monitored in vivo. This microsensing system may be applied to analyze pharmacokinetics and pharmacodynamics of various drugs at local sites.