Experimental hepatobiliary injury. Comparison of in vivo drug elimination with in vitro drug-metabolizing enzyme capacity in the rat

The effect of experimental hepatobiliary injury on drug metabolism was studied in a series ofin vivo andin vitro experiments in rats.In vivo aminopyrine elimination was measured by14CO2 breath analysis. This measure was compared with anin vitro estimate of the drug-metabolizing enzyme capacity of the whole liver (aminopyrine-free intrinsic clearance, Vmax/Km). The degree of hepatobiliary injury was measured by means of BSP biliary excretion. Two surgical models were studied: severe (complete bile duct obstruction) and mild (selective bile duct obstruction); as well as two drug-induced models: severe (alpha-naphthylisothiocyanate, ANIT) and mild (ethinyl estradiol). In the surgical models, only the complete-bile-duct-obstructed rat had a significantly decreased breath elimination rate of14CO2, 58% of control (P