EFFECTS OF PHENOBARBITAL ON BILE SALT METABOLISM IN CHOLESTASIS DUE TO INTRAHEPATIC BILE DUCT HYPOPLASIA

Abstract

The effects of phenobarbital (PB) on bile salt metabolism in a patient with severe cholestasis due to congenital paucity of perilobular bile ducts were studied with 14C-cholate and 3H-chenodeoxycholate. During the control period (without PB) cholate was the predominant bile salt in the peripheral blood, whereas chenodeoxycholate was predominant in the total bile salt pool. This difference in the distribution of the two primary bile salts appeared to be caused by relatively greater impairment of excretion of cholate from the liver cell into the bile. PB administration caused a decrease in the total serum bile salt concentration (from 132 to 62µg/ml), in the total bile salt pool (from 412 to 304 mg) and in the biologic half-life (cholate from 106 to 34 hours; chenodeoxycholate from 77 to 42 hours). The proportion of the total bile salt pool present in the peripheral blood decreased from 16.8% to 11.7%. In addition, PB markedly increased the fecal bile salt excretion. These data suggest the PB improves pruritus in this type of intrahepatic cholestasis by reducing serum bile salt concentrations. This is accomplished by a shift in bile salts from the peripheral blood into the enterohepatic circulation and by enhancing fecal bile salt excretion.