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Evaluation of changes in hepatic disposition of phenolsulfonphthalein, indocyanine green and fluorescein isothiocyanate-dextran at low temperatures using a rat liver perfusion system


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Title: Evaluation of changes in hepatic disposition of phenolsulfonphthalein, indocyanine green and fluorescein isothiocyanate-dextran at low temperatures using a rat liver perfusion system
Authors: Miyamoto, Hirotaka / Miyake, Hideaki / Yoshikawa, Naoki / Hirata, Haruna / Ohwaki, Yuichi / Fumoto, Shintaro / Sasaki, Hitoshi / Nakamura, Junzo / Nishida, Koyo
Issue Date: Jun-2012
Publisher: Pharmaceutical Press
Citation: Journal of Pharmacy and Pharmacology, 64(6), pp.848-854; 2012
Abstract: 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.
Keywords: hepatic disposition / indocyanine green / liver perfusion / phenolsulfonphthalein / therapeutic hypothermia
URI: http://hdl.handle.net/10069/35850
ISSN: 00223573
DOI: 10.1111/j.2042-7158.2012.01478.x
Rights: © 2012 Royal Pharmaceutical Society / This is the peer reviewed version of the following article: Journal of Pharmacy and Pharmacology, 64(6), pp.848-854; 2012, which has been published in final form at http://dx.doi.org/10.1111/j.2042-7158.2012.01478.x This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/35850

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