| New Lipid Modulating Drugs: The Role of Microsomal Transport Protein Inhibitors. | |
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MedLine Citation:
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PMID: 21418029 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Microsomal triglyceride transfer protein (MTP) is involved in the synthesis of very low density lipoprotein in the liver. Its deficiency results in abetalipoproteinemia. MTP inhibitors target the assembly and secretion of apolipoprotein B-containing lipoproteins. These agents may potentially play a role, alone or in combination, in the treatment of hypercholesterolemia or hypertriglyceridaemia. Clinical applications of MTP inhibitors initially focused primarily on high-dose monotherapy in order to produce substantial reductions in LDL-cholesterol levels but these proved to induce significant hepatic steatosis and transaminase elevations. However, likely orphan indications for MTP inhibitors, where a different risk-benefit profile applies, include patients with homozygous familial hypercholesterolemia where statins often show a low response. Development of MTP inhibitors has continued with some starting to enter clinical trials at lower doses or in formulations aimed at utilizing their efficacy while avoiding their side effects. These have shown promising results in reducing cholesterol, triglycerides and apolipoprotein B with a far lower incidence of, often, transient side-effects. The clinical efficacy and safety of MTP inhibition in patients with hyperlipidaemia remains to be fully determined and to be proven in both surrogate and clinical endpoint trials but there may be a role for these agents in orphan indications for rarer severe hyperlipidaemias. |
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Authors:
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Manfredi Rizzo; Anthony S Wierzbicki |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-22 |
Journal Detail:
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Title: Current pharmaceutical design Volume: - ISSN: 1873-4286 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9602487 Medline TA: Curr Pharm Des Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Dipartimento di Medicina Interna e Specialistica DIMIS Universita' di Palermo Via del Vespro, 141 - 90127 - Palermo, Italy. mrizzo@unipa.it. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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