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• W2020478826 abstract "The hypocholesterolemic and metabolic effects of ketoconazole (400 mg/d) alone (inhibits cholesterol synthesis at 14α-demethylation of lanosterol) and in combination with cholestyramine (12 g/d), were studied in nine women with xanthomatous familial hypercholesterolemia (FH). In addition to serum lipoprotein levels, cholesterol precursors, fecal steroids, and cholesterol absorption were measured before and during the drug treatments. Serum total and low-density lipoprotein (LDL)-cholesterol were reduced by 19% and 22% with ketoconazole; the respective changes were 16% and 21% for cholestyramine, and 31% and 41% for the combined ketoconazole and cholestyramine treatment. Serum triglycerides, very-low-density lipoprotein (VLDL)-and high-density lipoprotein (HDL)-cholesterol levels were unchanged. Accumulation of cholesterol precursors in serum suggested that ketoconazole inhibited cholesterol synthesis at Δ8-sterol levels. Serum and fecal lanosterols were increased up to 20-fold and were interrelated. Their maximal serum levels was 1.3 mg/DL and the lanosterol contents were negatively related to the serum cholesterol levels. The intestinal absorption and total intestinal fluxes of cholesterol were reduced by 27% and 29%. Cholesterol and bile acid synthesis were decreased by ketoconazole only when combined with cholestyramine. The synthesis of chenodeoxycholic acid was deeply hindered by ketoconazole. Thus, ketoconazole efficiently lowers serum total and LDL-cholesterol levels in FH patients, probably by inhibiting cholesterol synthesis and absorption. Effective biliary and fecal outputs of cholesterol precusors prevent their excessive increase in serum. Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase and cholesterol 7α-hydroxylase activities are detectably inhibited by ketoconazole only in combination with cholestyramine-induced enhancement of cholesterol and bile acid synthesis, although the enzyme activities still remain upregulated. Chenodeoxycholic acid production is consistently inhibited by ketoconazole." @default.
• W2020478826 created "2016-06-24" @default.
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• W2020478826 date "1991-01-01" @default.
• W2020478826 modified "2023-10-01" @default.
• W2020478826 title "Hypolipidemic effect and mechanism of ketoconazole without and with cholestyramine in familial hypercholesterolemia" @default.
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• W2020478826 doi "https://doi.org/10.1016/0026-0495(91)90189-4" @default.
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