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Effects of short‐term treatment with pravastatin on the hepatic synthesis of cholesterol and bile acids in gallstone patients
Author(s) -
Hillebrant,
Axelson,
Björkhem,
Hong Wang,
Lars Nyberg,
Einarsson
Publication year - 1998
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.1998.00288.x
Subject(s) - lathosterol , pravastatin , medicine , reductase , cholesterol , endocrinology , bile acid , hydroxymethylglutaryl coa reductase , hmg coa reductase , morning , chemistry , gastroenterology , enzyme , biochemistry , campesterol , sterol
Background HMG‐CoA reductase inhibitors are now the therapy of choice in the treatment of hypercholesterolaemia. The effects of long‐term treatment with these substances on plasma lipoproteins, cholesterol metabolism and biliary secretion of lipids have been extensively studied in humans. Much less is known about the effects of short‐term treatment. The aim of this study was to determine the time course of the effects 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 were included in the study. Except for the gallstone disease, these patients were otherwise 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 levels of lathosterol and 7α‐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 7α‐hydroxy‐4‐cholesten‐3‐one the activity of cholesterol 7α‐hydroxylase, the rate‐determining enzyme in bile acid synthesis. Results All treatment groups displayed a significant decrease in total cholesterol and low‐density lipoprotein (LDL)‐cholesterol, by about 12% and 17% respectively. Lathosterol was reduced by about 50% in all treatment groups. Of great interest was the finding that 7α‐hydroxy‐4‐cholesten‐3‐one was unaffected in all treatment groups. Conclusion The results show that short‐term pravastatin treatment in gallstone patients rapidly inhibits cholesterol synthesis and lowers plasma LDL‐cholesterol levels without effects on bile acid synthesis.