Effect of phenobarbital, spironolactone and pregnenolone-16α-carbonitrile on bile formation in the rat

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Abstract
The effects of pretreatment for 4 days with the hepatic microsomal enzyme inducers phenobarbital (8 mg/100 g body weight), spironolactone (20 mg/100 g body weight) and pregnenolone-16α-carbonitrile (7 mg/100 g body weight) on bile flow and bile lipid secretion have been compared in rats. Similar to phenobarbital, spironolactone and pregnenolone-16α-carbonitrile increased bile flow but did not alter bile salt excretion, indicating that these agents increased bile salt independent bile formation. This finding could be substantiated for spironolactone by studies of the relationship between bile salt excretion and bile flow during bile salt infusions. Whereas phenobarbital decreased cholesterol and phospholipid secretion to 39 and 49%, respectively, spironolactone and pregnenolone-16α-carbonitrile more than doubled cholestal excretion without influencing phospholipid output. As a consequence, marked differences in the effect on cholesterol saturation were observed: a decrease by phenobarbital and an increase following spironolactone and pregnenolone-16α-carbonitrile. The present studies demonstrate that different types of enzyme inducers may share certain effects on bile formation and differ in others.