A simplified isolated perfused rat liver apparatus: Characterization and measurement of extraction ratios of selected compounds

Vikram Sinha, Klaus Brendel, Michael Mayersohn

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Abstract

A simplified isolated perfused rat liver (IPRL) preparation has been developed and evaluated. The liver is briefly perfused in situ prior to being placed into a 37°C oven and suspended from a stand. This set-up takes about 5 min. A non-recirculatory or one-pass perfusion approach has been used. The performance of the apparatus was evaluated with use of three model compounds: antipyrine, lidocaine and ethanol. In addition, oxygen extraction was determined. The steady-state extraction ratio (ER) was determined for each compound (and oxygen) as a function of perfusate flow rate (15-35 ml/min) during sequential 45 min perfusion periods. Perfusion experiments lasted for up to 3 hr. The ERs (at 15 ml/min) of ethanol (0.65 ± 0.15), lidocaine (0.91 ± 0.01) and oxygen (0.65 ± 0.10) were dependent upon perfusate flow; whereas, antipyrine ER (0.07 ± 0.01) was independent of flow. The corresponding values for unbound intrinsic clearances (CL(u,int)) for antipyrine, ethanol, lidocaine and oxygen were: 1.6, 31.0, 158.0 and 27.5 ml/min, respectively. These findings are consistent with the known hepatic ER values for those compounds reported in the literature.

Original languageEnglish (US)
Pages (from-to)1795-1804
Number of pages10
JournalLife Sciences
Volume66
Issue number19
DOIs
Publication statusPublished - Mar 31 2000

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Keywords

  • Antipyrine
  • Ethanol
  • Extraction ratio
  • Intrinsic metabolic clearance
  • Isolated perfused rat liver
  • Lidocaine

ASJC Scopus subject areas

  • Pharmacology

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