@article{oai:nagasaki-u.repo.nii.ac.jp:00004709, author = {Miyamoto, Hirotaka and Miyake, Hideaki and Yoshikawa, Naoki and Hirata, Haruna and Ohwaki, Yuichi and Fumoto, Shintaro and Sasaki, Hitoshi and Nakamura, Junzo and Nishida, Koyo}, issue = {6}, journal = {Journal of Pharmacy and Pharmacology}, month = {Jun}, note = {Objectives The aim of this study was to determine the factor changing the hepatic disposition of a drug during hypothermia using a rat liver perfusion system. Methods The livers of male Wistar rats were perfused at 37, 32 or 28°C in the single-pass mode. Venous outflow dilution patterns and biliary excretion rate patterns of phenolsulfonphthalein (PSP), indocyanine green (ICG) and fluorescein isothiocyanate (FITC)-dextran (FD-4, MW 4400) after the injection of a bolus into the perfused rat liver were analysed based on statistical moment theory. Key findings The first-pass extraction ratio (E h) of PSP was significantly decreased at 32 and 28°C compared with 37°C. The biliary recovery of PSP and its conjugate was decreased and the biliary excretion was kept at a high concentration and was prolonged by low perfusion temperatures. ICG was almost extracted by a single-pass through the liver even at 32 and 28°C. The biliary recovery of ICG was significantly decreased at low temperature. Although the distribution volume of FD-4 as a vascular reference was not changed by perfusion temperature, the E h of FD-4 was decreased at 28°C although not markedly. Conclusion The change in hepatic disposition of a drug at low perfusion temperatures differed according to disposition processes under hypothermia., Journal of Pharmacy and Pharmacology, 64(6), pp.848-854; 2012}, pages = {848--854}, title = {Evaluation of changes in hepatic disposition of phenolsulfonphthalein, indocyanine green and fluorescein isothiocyanate-dextran at low temperatures using a rat liver perfusion system}, volume = {64}, year = {2012} }