Effects of ketoconazole on cholesterol precursors and low density lipoprotein kinetics in hypercholesterolemia.
Ketoconazole, an inhibitor of cholesterol synthesis at 14 alpha-demethylation of lanosterol, effectively reduces serum total and low density lipoprotein (LDL) cholesterol levels. We studied the effects of ketoconazole (400 mg/day for 5 weeks) on serum lipids, free and esterified noncholesterol stero...
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| Format: | Article |
| Language: | English |
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Elsevier
1993-01-01
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| Series: | Journal of Lipid Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520413197 |
| _version_ | 1818827676832497664 |
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| author | H Gylling H Vanhanen TA Miettinen |
| author_facet | H Gylling H Vanhanen TA Miettinen |
| author_sort | H Gylling |
| collection | DOAJ |
| description | Ketoconazole, an inhibitor of cholesterol synthesis at 14 alpha-demethylation of lanosterol, effectively reduces serum total and low density lipoprotein (LDL) cholesterol levels. We studied the effects of ketoconazole (400 mg/day for 5 weeks) on serum lipids, free and esterified noncholesterol sterols, and kinetics of LDL apolipoprotein B (apoB) in seven patients with heterozygous familial hypercholesterolemia (FH) and in three patients with primary hypercholesterolemia (nonFH). The total, intermediate density, and LDL cholesterol levels were significantly reduced by 24, 27, and 29%, respectively, and LDL apoB by 23%. Serum total and lipoprotein triglycerides were unchanged. The LDL cholesterol/apoB ratio decreased significantly. Serum ratios of lanosterols to cholesterol were increased over 50 times, almost the same in all lipoproteins and mainly as the unesterified form; free delta 8-precursor sterols, 2-5 times; cholestanol, slightly; while ratios of lanosterol of desmosterol, lathosterol, and plant sterols were virtually unchanged. Inconsistent esterification of methyl sterols might indicate unaltered acyl CoA:cholesterol acyltransferase activity. LDL apoB transport was decreased in all nonFH subjects but inconsistently in FH. The fractional catabolism rate (FCR) for LDL apoB was increased significantly in FH by 13% and inconsistently by 4% in nonFH. In a subgroup of three FH patients, more dense LDL (d 1.037-1.055 g/ml) was transported and catabolized faster on than off ketoconazole so that the serum level of this more dense LDL subfraction was unchanged, the decrease of LDL being due to a reduction of the less dense LDL subfraction.(ABSTRACT TRUNCATED AT 250 WORDS) |
| first_indexed | 2024-12-19T00:47:21Z |
| format | Article |
| id | doaj.art-862050d9991941ada10eeb48907a4980 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-19T00:47:21Z |
| publishDate | 1993-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-862050d9991941ada10eeb48907a49802022-12-21T20:44:13ZengElsevierJournal of Lipid Research0022-22751993-01-013415967Effects of ketoconazole on cholesterol precursors and low density lipoprotein kinetics in hypercholesterolemia.H Gylling0H Vanhanen1TA Miettinen2Second Department of Medicine, University of Helsinki, Finland.Second Department of Medicine, University of Helsinki, Finland.Second Department of Medicine, University of Helsinki, Finland.Ketoconazole, an inhibitor of cholesterol synthesis at 14 alpha-demethylation of lanosterol, effectively reduces serum total and low density lipoprotein (LDL) cholesterol levels. We studied the effects of ketoconazole (400 mg/day for 5 weeks) on serum lipids, free and esterified noncholesterol sterols, and kinetics of LDL apolipoprotein B (apoB) in seven patients with heterozygous familial hypercholesterolemia (FH) and in three patients with primary hypercholesterolemia (nonFH). The total, intermediate density, and LDL cholesterol levels were significantly reduced by 24, 27, and 29%, respectively, and LDL apoB by 23%. Serum total and lipoprotein triglycerides were unchanged. The LDL cholesterol/apoB ratio decreased significantly. Serum ratios of lanosterols to cholesterol were increased over 50 times, almost the same in all lipoproteins and mainly as the unesterified form; free delta 8-precursor sterols, 2-5 times; cholestanol, slightly; while ratios of lanosterol of desmosterol, lathosterol, and plant sterols were virtually unchanged. Inconsistent esterification of methyl sterols might indicate unaltered acyl CoA:cholesterol acyltransferase activity. LDL apoB transport was decreased in all nonFH subjects but inconsistently in FH. The fractional catabolism rate (FCR) for LDL apoB was increased significantly in FH by 13% and inconsistently by 4% in nonFH. In a subgroup of three FH patients, more dense LDL (d 1.037-1.055 g/ml) was transported and catabolized faster on than off ketoconazole so that the serum level of this more dense LDL subfraction was unchanged, the decrease of LDL being due to a reduction of the less dense LDL subfraction.(ABSTRACT TRUNCATED AT 250 WORDS)http://www.sciencedirect.com/science/article/pii/S0022227520413197 |
| spellingShingle | H Gylling H Vanhanen TA Miettinen Effects of ketoconazole on cholesterol precursors and low density lipoprotein kinetics in hypercholesterolemia. Journal of Lipid Research |
| title | Effects of ketoconazole on cholesterol precursors and low density lipoprotein kinetics in hypercholesterolemia. |
| title_full | Effects of ketoconazole on cholesterol precursors and low density lipoprotein kinetics in hypercholesterolemia. |
| title_fullStr | Effects of ketoconazole on cholesterol precursors and low density lipoprotein kinetics in hypercholesterolemia. |
| title_full_unstemmed | Effects of ketoconazole on cholesterol precursors and low density lipoprotein kinetics in hypercholesterolemia. |
| title_short | Effects of ketoconazole on cholesterol precursors and low density lipoprotein kinetics in hypercholesterolemia. |
| title_sort | effects of ketoconazole on cholesterol precursors and low density lipoprotein kinetics in hypercholesterolemia |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520413197 |
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