Effect of phenobarbital on bile salts in cholestasis

Abstract

Phenobarbital (PB) reduces pruritis in children with cholestasis. Individual bile salts were determined before and during PB treatment in 3 children with intrahepatic cholestasis (2 with benign recurrent cholestasis, 1 with paucity of intrahepatic bile duets) and in 3 with extrahepatic bilary atresia. In intrahepatic cholestasis the cholate/chenodeoxycholate ratio in serum, bile and urine was 2.5–10. Total serum bile salt concentration was 100–400 μg/ml. After 4 days on PB (10 mg/kg/day) total serum bile salts decreased dramatically to 1–10 μg/ml with concomitant disappearance of pruritus. Daily urinary bile salt excretion declined concomitantly from 15–40 mg to 1–2 mg. In contrast, in extrahepatic cholestasis, the cholate/chenodeoxycholate ratios were 0.1–0.4 in blood, bile and urine. Total serum bile salt concentration was 60–130 μg/ml. Treatment with PB did not lower serum or urinary bile salt concentrations. Thus, the ratio of cholate/chenodeoxycholate is different in intrahepatic and extrahepatic cholestasis. PB greatly enhances the removal of bile salts from blood in two types of intrahepatic cholestasis, but is ineffective in extrahepatic cholestasis. The simultaneous decrease in serum and urinary bile salt concentrations suggests that PB stimualtes the biliary excretion of bile salts.