An in vivo rat model for assessment of extrahepatic metabolism

Introduction: Xenobiotic metabolism in extrahepatic tissues has been extensively studied in vitro, but it is difficult to estimate in vivo the share of xenobiotic transformation in extrahepatic tissues for lack of a suitable approach. In this paper an in vivo rat model for assessment of extrahepatic metabolism is described, and the model was investigated using the conversion of lidocaine to monoethylglycinexylidide (MEGX). Methods: The rats were anesthetized with ethyl ether inhalation. The liver was exposed, the liver artery ligated, and the portal vein was clamped at its distal end. The left hepatic lobe was partly excised along its inferior margin, and a heparinized silicone catheter, diameter 0.2 cm, was inserted into the portal and left hepatic veins to allow the recirculation of portal vein blood. A sham operation was performed in the control group. Results: Phenol red test showed that hepatic blood supply was absolutely blocked in model rats. At 30 min after establishing the portal-cavum bypass, the renal function and electrolytes did not change, but serum glucose decreased by 64.4 +/- 30.4%; 30 min after intravenous administration of 1.0% lidocaine 2 mg.kg(-1) serum MEGX was 32.0 +/- 7.14% of that in the control group, which mostly existed in a free form and was not induced by phenobarbital pretreatment. Discussion: The model is easy to establish and provides an in vivo method to study the extrahepatic metabolism of xenobiotics. (C) 2002 Elsevier Science Inc. All rights reserved.