Pharmacokinetic Analysis of Free Radicals by in vivo BCM (Blood Circulation Monitoring)-ESR Method |
| |
Authors: | Koji Takechi Hideyuki Tamura Kiyoshi Yamaoka Hiromu Sakurat |
| |
Institution: |
a Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Nakauchi-cho 5, Yamashinaku, Kyoto, Japan
b Department of Analitical Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Shimoadachi-cho, Sakyo-ku, Kyoto, Japan |
| |
Abstract: | In pharmacokinetic studies, a variety of analytical method including radioisotopic detection and HPLC (high performance liquid chromatography) has been used. In the present investigation, we developed in vivo BCM (Blood Circulation Monitoring)-ESR method, which is a new technique with a conventional X-band ESR spectrometer for observing stable free radicals in the circulating blood of living rats under anaesthesia. Both 5-(PROXYL derivatives) and 6-(TEMPO derivatives) membered nitroxide spin probes with various types of substituent functional group were used. After physicochemical properties of the spin probes such as hyperfine coupling constant (A-value), g-value and partition coefficient as well as chemical stability of the compounds in the fresh blood were obtained, the in vivo BCM-ESR method was performed in normal rats. Several pharmacokinetic parameters such as half-life of the probes, distribution volume, total body clearance and mean residence time were obtained and discussed in terms of their chemical structures. In addition, clearance of a spin probe was related to the urine concentration. The BCM-ESR method was found to be very useful to observe free radicals at the real time. By time-dependent ESR signal decay of spin probes, pharmacokinetic parameters were obtained. |
| |
Keywords: | X-band ESR blood circulation monitoring nitroxide radicals rat pharmacokinetics radical clearance |
本文献已被 InformaWorld 等数据库收录! |
|