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 developed and evaluated. The liver is briefly perfused in situ prior to being placed 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 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 (CLu,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.
Sinha
V
V
Department of Pharmacy Practice, College of Pharmacy, The University of Arizona, Tucson 85721, USA.
Brendel
K
K
Mayersohn
M
M
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism; D000983:Antipyrine / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000378:metabolism; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D000431:Ethanol / Q000378:metabolism; D066298:In Vitro Techniques; D008012:Lidocaine / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion / Q000295:instrumentation*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000889:Anti-Arrhythmia Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002492:Central Nervous System Depressants; D000431:Ethanol; D008012:Lidocaine; D000983:Antipyrine