EFFECTS OF PHENOBARBITAL ON BILIARY LIPID-METABOLISM IN CHOLESTEROL GALLSTONE SUBJECTS

The effect of 1.7-2.2 mg/day oral phenobarbital over short (1 MO) and long term (6-24 MO) treatment on primary bile acid (BA) secretion, composition, synthesis, pool size, and enterohepatic cycling rates as well as phospholipid (PL) and cholesterol (C) secretion rates and biliary composition was determined in 12 asymptomatic cholesterol gallstone subjects while 5 normals had only short term studies. Phenobarbital enhanced BA and C secretion (BA-636±166 to 2110±382 mg/hr, p<0.001 and C-42±5 to 224±48 mg/hr, p<0.001) and BA cycling rate in all subjects studied during stimulated enterohepatic circulation but, during fasting, it only enhanced BA secretion (451±129 vs. 759±159 mg/hr, p<0.05) in gallstone subjects. Cholic acid (CA) production rate (171±28 to 395±9 mg/hr, p<0.05) and pool size (727±80 to 1209±132 mg/hr, p<0.05) were increased during long term treatment of gallstone subjects, while the proportion of CA in bile and deoxycholic acid (DCA) in feces increased. Treatment decreased biliary cholesterol from supersaturated to saturated levels (9.5±0.6 vs. 6.1±0.9 moles%, p<0.02) in all fasting gallstone subjects and decreased cholesterol crystal loads during long term treatment; but, while prohibiting gallstone growth, it did not affect stone dissolution over 24 month's treatment. Phenobarbital also failed to affect biliary lipid composition or bile acid pool size in short term treatment of normals. Thus, phenobarbital affected hepatic metabolism of CA by enhancing production rate, secretion, and pool size; and in testinal metabolism of both CA and chenodeoxycholic (CDC) acids by increasing their cycling rates. Phenobarbital may have failed to produce stone dissolution by enhancing CA production and pool size more than that of CDC. © 1979 American Oil Chemists' Society.