Effects of lovastatin and chenodiol on bile acid synthesis, bile lipid composition, and biliary lipid secretion in healthy human subjects.
To assess the relationship between cholesterol synthesis and feedback inhibition of bile acid synthesis, we studied seven normal human subjects taking three different doses of chenodiol, 0, 5, and 15 mg/kg per day: once while taking no lovastatin and again while taking lovastatin 80 mg/day. Lovastatin and both doses of chenodiol significantly lowered bile acid synthesis measured by the 14CO2 method, but there was no significant interaction between the perturbations. Both also lowered cholesterol saturation index of gallbladder bile without appreciable interaction, and the combination was distinctly more effective than either medication alone. Lovastatin and low-dose chenodiol both lowered biliary cholesterol secretion without affecting bile acid secretion. Increasing the dose of chenodiol did not further lower cholesterol secretion, but did further reduce saturation index because of an increase in secretion of bile acid and phospholipid. These studies indicate that there is no interaction between cholesterol synthesis and feedback return of bile acid in the enterohepatic circulation with respect to either bile acid synthesis or biliary lipid secretion; that the combination of chenodiol and lovastatin is better than either alone for improving biliary cholesterol saturation; and that the mechanism by which chenodiol lowers cholesterol saturation is dose-dependent.
Hanson
D S
DS
Department of Medicine, Veterans Affairs Medical Center, Minneapolis, MN 55417.
Duane
W C
WC
D000368:Aged; D001646:Bile / Q000737:chemistry / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D002635:Chenodeoxycholic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006801:Humans; D008148:Lovastatin / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000378:metabolism
D001647:Bile Acids and Salts; D004338:Drug Combinations; D010743:Phospholipids; D002635:Chenodeoxycholic Acid; D002784:Cholesterol; D008148:Lovastatin