Barbiturate-Induced Choleresis: Possible Independence from Microsomal Enzyme Induction

The influence of four barbiturates, phenobarbital, barbital, thiopental, and pentobarbital, on bile secretion and on the hepatic microsomal system was studied in anesthetized rats. The barbiturates were injected intraperitoneally for 4 days and the animals were studied on the 5th day. It was found that: (1) phenobarbital, barbital, and thiopental, but not pentobarbital, significantly increased liver weight, cytochrome P-450 concentration in the liver, decreased pentobarbital sleeping time and induced a hypertrophy of the smooth endoplasmic reticulum in the hepatocytes at electron microscopy; (2) in contrast, the four barbiturates, including pentobarbital, significantly increased bile flow; this increase was attributed to an increase in the bile acid independent bile flow. There was no correlation between the increase in bile flow and the cytochrome P-450 concentration in the liver. It is concluded that the increase in bile flow observed after barbiturate treatment in the rat is possibly independent of the hepatic microsomal enzyme induction produced by these drugs.