Journal of Lipid Research, Vol 35, 1462-1468, Copyright © 1994 by Lipid Research, Inc.
Effects of lovastatin and chenodiol on bile acid synthesis, bile lipid composition, and biliary lipid secretion in healthy human subjects
DS Hanson and WC Duane
Department of Medicine, Veterans Affairs Medical Center, Minneapolis, MN 55417.
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.
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