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. 1990 Mar;31(3):348–350. doi: 10.1136/gut.31.3.348

Effect of pravastatin on biliary lipid composition and bile acid synthesis in familial hypercholesterolaemia.

N Hoogerbrugge-vd Linden 1, F W de Rooy 1, H Jansen 1, M van Blankenstein 1
PMCID: PMC1378282  PMID: 2108908

Abstract

Nine patients with heterozygous familial hypercholesterolaemia were treated for eight weeks with either 40 mg pravastatin or placebo under double blind conditions. Six patients received pravastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Treatment with pravastatin resulted in a significant decrease in plasma cholesterol caused by a decrease in low density lipoprotein cholesterol (LDL-c) of 30% (p less than 0.005). We determined the effect of this medication on the lithogenicity of bile. Cholesterol saturation index of fasting gall bladder bile decreased with 23% (p less than 0.01) from 1.06 to 0.75 during treatment with pravastatin. A reduction of 24% (p less than 0.01) in molar percentage of biliary cholesterol was seen. After treatment the total bile acid excretion in faeces and the molar percentage of biliary bile acids were not significantly changed, suggesting that pravastatin does not influence bile acid biosynthesis to a significant extent. These findings indicate that treatment with pravastatin can decrease the incidence and complications of cholesterol gall stones.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bruusgaard A. Quantitative determination of the major 3-hydroxy bile acids in biological material after thin-layer chromatographic separation. Clin Chim Acta. 1970 Jun;28(3):495–504. doi: 10.1016/0009-8981(70)90078-1. [DOI] [PubMed] [Google Scholar]
  2. Carey M. C. Critical tables for calculating the cholesterol saturation of native bile. J Lipid Res. 1978 Nov;19(8):945–955. [PubMed] [Google Scholar]
  3. Duane W. C., Hunninghake D. B., Freeman M. L., Pooler P. A., Schlasner L. A., Gebhard R. L. Simvastatin, a competitive inhibitor of HMG-CoA reductase, lowers cholesterol saturation index of gallbladder bile. Hepatology. 1988 Sep-Oct;8(5):1147–1150. doi: 10.1002/hep.1840080531. [DOI] [PubMed] [Google Scholar]
  4. Grundy S. M., Bilheimer D. W. Inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase by mevinolin in familial hypercholesterolemia heterozygotes: effects on cholesterol balance. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2538–2542. doi: 10.1073/pnas.81.8.2538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Grundy S. M., Metzger A. L., Adler R. D. Mechanisms of lithogenic bile formation in American Indian women with cholesterol gallstones. J Clin Invest. 1972 Dec;51(12):3026–3043. doi: 10.1172/JCI107130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kempen H. J., De Lange J., Vos-Van Holstein M. P., Van Wachem P., Havinga R., Vonk R. J. Effect of ML-236B (compactin) on biliary excretion of bile salts and lipids, and on bile flow, in the rat. Biochim Biophys Acta. 1984 Jul 26;794(3):435–443. doi: 10.1016/0005-2760(84)90010-9. [DOI] [PubMed] [Google Scholar]
  7. Leiss O., von Bergmann K., Gnasso A., Augustin J. Effect of gemfibrozil on biliary lipid metabolism in normolipemic subjects. Metabolism. 1985 Jan;34(1):74–82. doi: 10.1016/0026-0495(85)90064-2. [DOI] [PubMed] [Google Scholar]
  8. Pertsemlidis D., Panveliwalla D., Ahrens E. H., Jr Effects of clofibrate and of an estrogen-progestin combination on fasting biliary lipids and cholic acid kinetics in man. Gastroenterology. 1974 Apr;66(4):565–573. [PubMed] [Google Scholar]
  9. Redgrave T. G., Roberts D. C., West C. E. Separation of plasma lipoproteins by density-gradient ultracentrifugation. Anal Biochem. 1975 May 12;65(1-2):42–49. doi: 10.1016/0003-2697(75)90488-1. [DOI] [PubMed] [Google Scholar]
  10. Tint G. S., Salen G., Shefer S. Effect of ursodeoxycholic acid and chenodeoxycholic acid on cholesterol and bile acid metabolism. Gastroenterology. 1986 Oct;91(4):1007–1018. doi: 10.1016/0016-5085(86)90708-0. [DOI] [PubMed] [Google Scholar]
  11. Tsujita Y., Kuroda M., Shimada Y., Tanzawa K., Arai M., Kaneko I., Tanaka M., Masuda H., Tarumi C., Watanabe Y. CS-514, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase: tissue-selective inhibition of sterol synthesis and hypolipidemic effect on various animal species. Biochim Biophys Acta. 1986 Jun 11;877(1):50–60. doi: 10.1016/0005-2760(86)90117-7. [DOI] [PubMed] [Google Scholar]
  12. Yoshino G., Kazumi T., Iwai M., Iwatani I., Matsuba K., Kasama T., Matsushita M., Otsuki M., Baba S. Effects of CS-514 on plasma lipids and lipoprotein composition in hypercholesterolemic subjects. Atherosclerosis. 1988 Jun;71(2-3):95–101. doi: 10.1016/0021-9150(88)90133-5. [DOI] [PubMed] [Google Scholar]

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