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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. 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. 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. The change in hepatic disposition of a drug at low perfusion temperatures differed according to disposition processes under hypothermia. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Citation

Hirotaka Miyamoto, Hideaki Miyake, Naoki Yoshikawa, Haruna Hirata, Yuichi Ohwaki, Shintaro Fumoto, Hitoshi Sasaki, Junzo Nakamura, Koyo Nishida. Evaluation of changes in hepatic disposition of phenolsulfonphthalein, indocyanine green and fluorescein isothiocyanate-dextran at low temperatures using a rat liver perfusion system. The Journal of pharmacy and pharmacology. 2012 Jun;64(6):848-54

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PMID: 22571263

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