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    
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.
F Lanzarotto; B Panarotto; R Sorbara; M Panteghini; F Pagani; S Sosta; A Lanzini
Related Documents :
2338194 - Lovastatin added to ursodeoxycholic acid further reduces biliary cholesterol saturation.
12153554 - Effects of combined treatment with pravastatin and ursodeoxycholic acid on hepatic chol...
4018504 - Metabolism of lithocholic and chenodeoxycholic acids in the squirrel monkey.
8659944 - Obagi's modified trichloroacetic acid (tca)-controlled variable-depth peel: a study of ...
17640004 - Structure elucidation and complete nmr spectral assignments of three new lanostanoid tr...
1010844 - Ribonucleases from porcine brain. partial purification and properties.
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    
Gastroenterology Unit, Spedali Civili and Medical School, Brescia, Italy.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
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
Hypercholesterolemia / blood,  drug therapy*,  metabolism
Lipids / blood
Lipoproteins, HDL / blood
Lipoproteins, LDL / blood
Middle Aged
Simvastatin / therapeutic use*
Ursodeoxycholic Acid / therapeutic use*
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

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

Previous Document:  Immunoreactive pancreatic Reg protein in sera from cystic fibrosis patients with and without pancrea...
Next Document:  The role of apolipoprotein E and glucose intolerance in gallstone disease in middle aged subjects.