Linked Life Data

3356951

Source:http://linkedlifedata.com/resource/pubmed/id/3356951

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1988-5-24
pubmed:abstractText
Ketoconazole, an antifungal antibiotic, inhibits cholesterol synthesis by blocking demethylation of lanosterol. Effects of this inhibition were studied on serum cholesterol, lipoproteins and cholesterol precursors, biliary lipid composition, and fecal steroid elimination in five patients with prostate cancer treated with large doses of ketoconazole. The serum level of total cholesterol fell by 27%, that of LDL cholesterol by 41% and that of LDL apoB by 32% with ketoconazole alone; the fall in the total cholesterol level of a patient treated with ketoconazole-cholestyramine was 65%. Serum contents of free lanosterol and dihydrolanosterol increased up to 250 times, yet the total concentrations remained less than 2 mg/dl. Of the other cholesterol precursor sterols only those with delta 8-double bond increased several times, indicating that in addition to 14 alpha-demethylation, ketoconazole also interfered with metabolism of later intermediary sterols to some extent. Compared with serum sterols, lanosterols were enriched in biliary and fecal sterols up to 10-20 times. Fecal lanosterol output increased from 12 to 247 mg/day, and comprised over 20% fecal steroids of endogenous origin. Bile acid synthesis was significantly decreased, the proportion of chenodeoxycholic acid being markedly reduced in both biliary and fecal bile acids. Cholesterol absorption appeared to decrease yet fecal neutral sterol output and cholesterol synthesis were unchanged and the overall sterol synthesis was increased. It thus appears that ketoconazole inhibits cholesterol elimination as bile acids. However, by blocking 14 alpha-demethylation, it results in effective drainage of sterol nucleus as lanosterols into bile and feces, which, in turn, is associated with a marked reduction in low density lipoprotein (LDL) cholesterol level probably through activation of hepatic LDL apoB receptors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-2275
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
43-51
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Cholesterol metabolism during ketoconazole treatment in man.
pubmed:affiliation
Second Department of Medicine, University of Helsinki, Finland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't