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  • Title: Comparative effects of lovastatin and chenodeoxycholic acid on plasma cholestanol levels and abnormal bile acid metabolism in cerebrotendinous xanthomatosis.
    Author: Salen G, Batta AK, Tint GS, Shefer S.
    Journal: Metabolism; 1994 Aug; 43(8):1018-22. PubMed ID: 8052141.
    Abstract:
    We investigated the effect of the hepatic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor lovastatin and the primary bile acid chenodeoxycholic acid (CDCA) on plasma sterol and bile alcohol concentrations and the excretion of bile alcohols in urine in a 38-year-old homozygote with cerebrotendinous xanthomatosis (CTX). Untreated, plasma cholesterol concentrations were less than normal (171 +/- 5 v 185 +/- 3 mg/dL, P < .05) while plasma cholestanol levels were more than 20 times higher than the control mean (2.26 +/- 0.17 v 0.1 +/- 0.1 mg/dL, P < .0001). Plasma and urinary bile alcohol concentrations were markedly increased (12.6 +/- 0.6 and 154 micrograms/mL, respectively, v trace amounts in controls), with the ratio of 5 beta-cholestane-3 alpha,7 alpha,12 alpha, 25-tetrol to 5 beta-cholestane, 3 alpha,7 alpha,12 alpha,23 (22 and 24),25-pentols being 1.6 in plasma and reversed to 0.15 in urine. Treatment with lovastatin (40 mg/d) reduced plasma cholesterol concentrations 13%, but failed to decrease plasma cholestanol or bile alcohol levels. Abundant amounts of bile alcohols continued to be excreted in urine. In contrast, CDCA (750 mg/d) inhibited abnormal bile acid synthesis, as evidence by a 17-fold decrease in total bile alcohol levels in plasma and a 29-fold decrease in urine and the virtual elimination of cholic acid and deoxycholic acid from the bile. Plasma cholestanol concentrations also decreased 85%, but cholesterol levels increased 14%. The combination of CDCA with lovastatin did not improve plasma cholestanol or bile alcohol concentrations compared with CDCA treatment alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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