| Lifibrol as a model compound for a novel lipid-lowering mechanism of action. | |
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MedLine Citation:
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PMID: 20693157 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Lifibrol is a potent lipid-lowering drug with an unknown mechanism of action. We investigated its effects on lipoprotein and sterol metabolism in normocholesterolemic male participants. Seven participants were treated for 4 weeks with 600 mg/d lifibrol and 9 with 40 mg/d pravastatin in a double-blind randomized parallel-group trial. Kinetic studies were performed at baseline and under acute and chronic treatment. Turnover of apolipoprotein B-100 was investigated with endogenous stable-isotope labeling, and kinetic parameters were derived by multicompartmental modeling. Lathosterol and cholesterol metabolism were investigated using mass isotopomer distribution analysis (MIDA) after [1-(13)C]acetate labeling. Carbon metabolism was investigated by calculating the total isotope incorporation into newly formed sterols and measuring the disposal of acetate by (13)CO(2) breath analysis. Total- and low-density lipoprotein (LDL) cholesterol decreased by 18% and 27% under lifibrol and by 17% and 28% under pravastatin, respectively, whereas very-low-density lipoprotein (VLDL) cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol did not change. Very-low-density lipoprotein apoB fractional synthesis and production increased under lifibrol but remained unchanged under pravastatin. Low-density lipoprotein apoB fractional synthesis and production increased under pravastatin but remained unchanged under lifibrol. Mass isotopomer distribution analysis indicated that both drugs decrease endogenous sterol synthesis after acute administration, but pravastatin had more powerful effects. Carbon-13 appearance in breath was higher during pravastatin than during lifibrol treatment. Mass isotopomer distribution analysis and carbon metabolism analysis indicated compartmentalization at the site of sterol synthesis, thus suggesting differential effects of the 2 drugs. Although having comparable lipid-lowering properties, lifibrol seems to have a mechanism of action distinct from that of statins. Lifibrol could serve as a model compound for the development of new lipid-lowering agents. |
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Authors:
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Heiner K Berthold; Thomas Sudhop; Klaus von Bergmann; Ioanna Gouni-Berthold |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-06 |
Journal Detail:
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Title: Journal of cardiovascular pharmacology and therapeutics Volume: 15 ISSN: 1940-4034 ISO Abbreviation: J. Cardiovasc. Pharmacol. Ther. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-24 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9602617 Medline TA: J Cardiovasc Pharmacol Ther Country: United States |
Other Details:
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Languages: eng Pagination: 364-72 Citation Subset: IM |
Affiliation:
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Department of Clinical Pharmacology, University of Bonn, Bonn, Germany. heiner.berthold@charite.de |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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