title: Evaluation of changes in hepatic disposition of phenolsulfonphthalein, indocyanine green and fluorescein isothiocyanate-dextran at low temperatures using a rat liver perfusion system.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The change in hepatic disposition of a drug at low perfusion temperatures differed according to disposition processes under hypothermia.
authors.affiliation: Graduate School of Biomedical Sciences, Nagasaki University             Department of Hospital Pharmacy, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Miyamoto
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyake
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshikawa
authors.forename: Haruna
authors.initials: H
authors.lastname: Hirata
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ohwaki
authors.forename: Shintaro
authors.initials: S
authors.lastname: Fumoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Junzo
authors.initials: J
authors.lastname: Nakamura
authors.forename: Koyo
authors.initials: K
authors.lastname: Nishida
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D003080:Cold Temperature; D003911:Dextrans / Q000493:pharmacokinetics*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D007036:Hypothermia, Induced; D008658:Inactivation, Metabolic; D007208:Indocyanine Green / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010637:Phenolsulfonphthalein / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate; D010637:Phenolsulfonphthalein; D007208:Indocyanine Green