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Abstract
To determine if ketoconazole influences cholesterol metabolism in humans, plasma lipid levels were studied in seven men with advanced prostate cancer who were being treated with high-dose ketoconazole. Additionally, the effects of ketoconazole on cholesterol synthesis in cultured normal human fibroblasts were studied. High-dose ketoconazole therapy caused a 27 percent reduction in total serum cholesterol values without affecting serum triglyceride levels. The reduction in serum cholesterol levels was maintained for five months in six of seven patients. The fall in total cholesterol levels was due to a 38 percent reduction in low-density lipoprotein cholesterol levels without associated changes in high-density lipoprotein cholesterol levels. Serum lanosterol levels increased 46 percent during ketoconazole treatment. Studies in cultured normal human fibroblasts showed that ketoconazole inhibited cholesterol synthesis by blocking the conversion of lanosterol to cholesterol. These results establish that ketoconazole is a potent inhibitor of cholesterol production in vivo and in vitro.
View details for Web of Science ID A1986A879200014
View details for PubMedID 3754384