Document Detail


Effect of long term simvastatin administration as an adjunct to ursodeoxycholic acid: evidence for a synergistic effect on biliary bile acid composition but not on serum lipids in humans.
MedLine Citation:
PMID:  10075964     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Stimulated bile acid synthesis preferentially utilises newly synthesised cholesterol, raising the possibility that combination of simvastatin (an inhibitor of cholesterol synthesis) with ursodeoxycholic acid (UDCA; a stimulator of bile acid synthesis) may result in reduced bile acid synthesis and greater enrichment of the pool with UDCA than that achieved with UDCA treatment alone. AIMS: To investigate the effect of simvastatin and UDCA given alone and in combination on serum and biliary lipid and biliary bile acid composition. METHODS: Eighteen patients with primary non-familial hypercholesterolaemia were studied during treatment with simvastatin 20 mg/day, UDCA 10 mg/kg/day, and a combination of the two drugs. Each regimen was given in random order for three months following a three month lead in period. RESULTS: Simvastatin significantly reduced serum low density lipoprotein (LDL) cholesterol but biliary cholesterol concentration remained unchanged. Combination of the two drugs had no synergistic effect on serum cholesterol concentration, but significantly increased the proportion of UDCA in the bile acid pool from 35% during UDCA to 48% during combination treatment (p<0.04). CONCLUSIONS: Results showed that: (1) simvastatin reduces serum LDL cholesterol but has no effect on biliary cholesterol concentration, supporting the concept that newly synthesised cholesterol is not the preferential source for biliary cholesterol; and (2) combination of simvastatin with UDCA has the predicted effect of enhancing the proportion of UDCA in the pool. This effect may be of benefit in the treatment of cholestatic liver diseases.
Authors:
F Lanzarotto; B Panarotto; R Sorbara; M Panteghini; F Pagani; S Sosta; A Lanzini
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  Gut     Volume:  44     ISSN:  0017-5749     ISO Abbreviation:  Gut     Publication Date:  1999 Apr 
Date Detail:
Created Date:  1999-06-10     Completed Date:  1999-06-10     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2985108R     Medline TA:  Gut     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  552-6     Citation Subset:  AIM; IM    
Affiliation:
Gastroenterology Unit, Spedali Civili and Medical School, Brescia, Italy.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Anticholesteremic Agents / therapeutic use*
Bile / metabolism
Bile Acids and Salts / metabolism
Cholagogues and Choleretics / therapeutic use*
Cholesterol / metabolism
Cross-Over Studies
Double-Blind Method
Drug Synergism
Drug Therapy, Combination
Female
Humans
Hypercholesterolemia / blood,  drug therapy*,  metabolism
Lipids / blood
Lipoproteins, HDL / blood
Lipoproteins, LDL / blood
Male
Middle Aged
Simvastatin / therapeutic use*
Ursodeoxycholic Acid / therapeutic use*
Chemical
Reg. No./Substance:
0/Anticholesteremic Agents; 0/Bile Acids and Salts; 0/Cholagogues and Choleretics; 0/Lipids; 0/Lipoproteins, HDL; 0/Lipoproteins, LDL; 128-13-2/Ursodeoxycholic Acid; 57-88-5/Cholesterol; 79902-63-9/Simvastatin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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