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 subje cts 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 lower ed bile acid synthesis measured by the (CO2)-C-14 method, but there wa s no significant interaction between the perturbations. Both also lowe red cholesterol saturation index of gallbladder bile without appreciab le interaction, and the combination was distinctly more effective than either medication alone. Lovastatin and low-dose chenodiol both lower ed biliary cholesterol secretion without affecting bile acid secretion . Increasing the dose of chenodiol did not further lower cholesterol s ecretion, but did further reduce saturation index because of an increa se in secretion of bile acid and phospholipid. jlr These studies indic ate that there is no interaction between cholesterol synthesis and fee dback return of bile acid in the enterohepatic circulation with respec t to either bile acid synthesis or biliary lipid secretion; that the c ombination of chenodiol and lovastatin is better than either alone for improving biliary cholesterol saturation; and that the mechanism by w hich chenodiol lowers cholesterol saturation is dose-dependent.