Universität zu Köln

Berthold, Heiner K. ORCID: 0000-0002-1457-2216, Sudhop, Thomas, von Bergmann, Klaus and Gouni-Berthold, Ioanna (2010). Lifibrol as a Model Compound for a Novel Lipid-Lowering Mechanism of Action. J. Cardiovasc. Pharmacol. Ther., 15 (4). S. 364 - 373. THOUSAND OAKS: SAGE PUBLICATIONS INC. ISSN 1074-2484

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Abstract

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 [I -(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

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Berthold, Heiner K. UNSPECIFIED orcid.org/0000-0002-1457-2216 UNSPECIFIED Sudhop, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED von Bergmann, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Gouni-Berthold, Ioanna UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-491596
DOI:	10.1177/1074248410371100
Journal or Publication Title:	J. Cardiovasc. Pharmacol. Ther.
Volume:	15
Number:	4
Page Range:	S. 364 - 373
Date:	2010
Publisher:	SAGE PUBLICATIONS INC
Place of Publication:	THOUSAND OAKS
ISSN:	1074-2484
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LIPOPROTEIN APOLIPOPROTEIN B-100; LOW-DENSITY LIPOPROTEINS; MIXED HYPERLIPIDEMIA; METABOLISM; CHOLESTEROL; HYPERCHOLESTEROLEMIA; HUMANS; ATORVASTATIN; FENOFIBRATE; PRAVASTATIN Multiple languages Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49159