EFFECTS OF SHORT-TERM TREATMENT WITH PRAVASTATIN ON THE HEPATIC SYNTHESIS OF CHOLESTEROL AND BILE-ACIDS IN GALLSTONE PATIENTS

Background HMG-CoA reductase inhibitors are now the therapy of choice in the treatment of hypercholesterolaemia. The effects of long-term tr eatment with these substances on plasma lipoproteins, cholesterol meta bolism and biliary secretion of lipids have been extensively studied i n humans. Much less is known about the effects of short-term treatment . The aim of this study was to determine the rime course of the effect s of HMG-CoA reductase inhibitors on plasma lipoprotein levels as well as cholesterol and bile acid synthesis in gallstone patients. Methods Thirty-six patients undergoing elective cholecystectomy mere included in the study. Except for the gallstone disease, these patients were o therwise healthy Four groups of subjects were treated with the HMG-CoA reductase inhibitor pravastatin (Pravachol), 20 mg twice daily for 12 , 24, 48 and 72 h preoperatively. Plasma lipoproteins and plasma level s of lathosterol and 7 alpha-hydroxy-4-cholesten-3-one were determined before initiation of pravastatin treatment and on the morning of the day of the operation, lathosterol reflecting hepatic HMG-CoA reductase activity and 7 alpha-hydroxy-4-cholesten-3-one the activity of choles terol 7 alpha-hydroxylase, the rate-determining enzyme in bile acid sy nthesis. Results All treatment groups displayed a significant decrease in total cholesterol and low-density lipoprotein (LDL)-cholesterol, b y about 12% and 17% respectively. Lathosterol was reduced by about 50% in all treatment groups. Of great interest was the finding that 7 alp ha-hydroxy-4-cholesten-3-one was unaffected in all treatment groups. C onclusion The results show that short-term pravastatin treatment in ga llstone patients rapidly inhibits cholesterol synthesis and lowers pla sma LDL-cholesterol levels without effects on bile acid synthesis.