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

A simplified isolated perfused rat liver (IPRL) preparation has been develo ped and evaluated. The liver is briefly perfused in situ prior to being pla ced into a 37 degrees C oven and suspended from a stand. This set-up takes about 5 min. A non-recirculatory or one-pass perfusion approach has been us ed. The performance of the apparatus was evaluated with use of three model compounds: antipyrine, lidocaine and ethanol. In addition, oxygen extractio n 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 last ed for up to 3 hr. The ERs (at 15 ml/min) of ethanol (0.65 +/- 0.15), lidoc aine (0.91 +/- 0.01) and oxygen (0.65 +/- 0.10) were dependent upon perfusa te flow; whereas, antipyrine ER (0.07 +/- 0.01) was independent of flow. Th e corresponding values for unbound intrinsic clearances (CLu,int) for antip yrine, 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 val ues for those compounds reported in the literature.