lomitapide
{{Short description|Chemical compound}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 444364270
| image = Lomitapide_skeletal.svg
| pronounce =
| tradename = Juxtapid (US), Lojuxta (EU)
| Drugs.com =
| MedlinePlus =
| licence_EU = yes
| DailyMedID = Lomitapide
| licence_US = Lomitapide
| pregnancy_AU =
| pregnancy_category =
| routes_of_administration = By mouth
| ATC_prefix = C10
| ATC_suffix = AX12
| ATC_supplemental =
| legal_AU =
| legal_CA =
| legal_UK =
| legal_US = Rx-only
| legal_EU = Rx-only
| legal_status =
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life =
| excretion =
| index2_label = mesylate
| IUPHAR_ligand = 7439
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 182431-12-5
| CAS_number2 = 202914-84-9
| PubChem = 9853053
| PubChem2 = 11274333
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB08827
| DrugBank2 = DBSALT000110
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 8028764
| ChemSpiderID2 = 9449335
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 82KUB0583F
| UNII2 = X4S83CP54E
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D09637
| KEGG2 = D09638
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 72297
| ChEBI2 = 72299
| ChEMBL = 354541
| ChEMBL2 = 2105662
| synonyms = AEGR-773, BMS-201038
| IUPAC_name = N-(2,2,2-Trifluoroethyl)-9-[4-[4-
| C=39 | H=37 | F=6 | N=3 | O=2
| smiles = FC(F)(F)c5ccc(cc5)-c1ccccc1C(=O)NC4CCN(CC4)CCCCC2(C(=O)NCC(F)(F)F)c3ccccc3-c6ccccc26
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C39H37F6N3O2/c40-38(41,42)25-46-36(50)37(33-13-5-3-10-30(33)31-11-4-6-14-34(31)37)21-7-8-22-48-23-19-28(20-24-48)47-35(49)32-12-2-1-9-29(32)26-15-17-27(18-16-26)39(43,44)45/h1-6,9-18,28H,7-8,19-25H2,(H,46,50)(H,47,49)
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = MBBCVAKAJPKAKM-UHFFFAOYSA-N
}}
Lomitapide , sold under the brand name Juxtapid in the US and Lojuxta in the EU, is a medication used as a lipid-lowering agent for the treatment of familial hypercholesterolemia, developed by Aegerion Pharmaceuticals.{{cite journal
| author = H. Spreitzer
| date = 12 March 2007
| title = Neue Wirkstoffe – BMS-201038
| journal = Österreichische Apothekerzeitung
| issue = 6/2007
| pages = 268
| language = German
}} It has been tested in clinical trials as single treatment and in combinations with atorvastatin, ezetimibe and fenofibrate.{{cite journal | vauthors = Horwich TB, Fonarow GC | title = Measures of obesity and outcomes after myocardial infarction | journal = Circulation | volume = 118 | issue = 5 | pages = 469–71 | date = July 2008 | pmid = 18663098 | doi = 10.1161/CIRCULATIONAHA.108.792689 | doi-access = free }}{{cite web | url = http://www.pr-inside.com/aegerion-pharmaceuticals-inc-announces-aegr-r904473.htm | title = Aegerion Pharmaceuticals, Inc. Announces AEGR-733 Phase II Data Demonstrates Significant Lowering of LDL Cholesterol with Promising Hepatic Safety Profile | work = Business Wire | date = 9 November 2008 | archive-url = https://web.archive.org/web/20120229092512/http://www.pr-inside.com/aegerion-pharmaceuticals-inc-announces-aegr-r904473.htm | archive-date=2012-02-29 }}
The US Food and Drug Administration (FDA) approved lomitapide in December 2012, as an orphan drug to reduce LDL cholesterol, total cholesterol, apolipoprotein B, and non-high-density lipoprotein (non-HDL) cholesterol in people with homozygous familial hypercholesterolemia (HoFH).{{cite web | url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333285.htm | archive-url = https://web.archive.org/web/20130128180135/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333285.htm | archive-date = 28 January 2013 | title = FDA approves new orphan drug for rare cholesterol disorder | publisher = U.S. Food and Drug Administration }}
In July 2013, the European Commission approved lomitapide as an adjunct to a low-fat diet and other lipid-lowering medicinal products with or without low density lipoprotein (LDL) apheresis in adults with HoFH.{{cite web | title=Lojuxta EPAR | website=European Medicines Agency (EMA) | date=3 September 2013 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/lojuxta | access-date=27 January 2021}}
Mechanism of action
Lomitapide inhibits the microsomal triglyceride transfer protein (MTP or MTTP) which is necessary for very low-density lipoprotein (VLDL) assembly and secretion in the liver.{{cite journal | vauthors = Cuchel M, Bloedon LT, Szapary PO, Kolansky DM, Wolfe ML, Sarkis A, Millar JS, Ikewaki K, Siegelman ES, Gregg RE, Rader DJ | display-authors = 6 | title = Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia | journal = The New England Journal of Medicine | volume = 356 | issue = 2 | pages = 148–56 | date = January 2007 | pmid = 17215532 | doi = 10.1056/NEJMoa061189 | doi-access = free }}
In December 2012, drug manufacturer Aegerion announced they had been approved by the FDA to as "an adjunct to a low-fat diet and other lipid-lowering treatments...in patients with homozygous familial hypercholesterolemia (HoFH)."{{cite web|title=FDA Approves Juxtapid for Homozygous Familial Hypercholesteolemia|url=http://www.dailyrx.com/juxtapid-reduces-cholesterol-patients-homozygous-familial-hypercholesterolemia|date=26 December 2012|access-date=1 January 2013|archive-url=https://web.archive.org/web/20121229140605/http://www.dailyrx.com/juxtapid-reduces-cholesterol-patients-homozygous-familial-hypercholesterolemia|archive-date=29 December 2012|url-status=dead}}{{cite press release | url = http://ir.aegerion.com/releasedetail.cfm?ReleaseID=728650 | title = FDA Approves Aegerion Pharmaceuticals' Juxtapid (lomitapide) Capsules for Homozygous Familial Hypercholesterolemia (HoFH) | publisher = Aegerion Pharmaceuticals | date = 24 December 2012 | access-date = 1 January 2013 | archive-url = https://web.archive.org/web/20160922115515/http://ir.aegerion.com/releasedetail.cfm?releaseid=728650 | archive-date = 22 September 2016 | url-status = dead }}
Side effects
In a Phase III study, lomitapide led to elevated aminotransferase levels and fat accumulation in the liver.
References
{{Reflist}}
External links
- {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/lomitapide | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Lomitapide }}
{{Lipid modifying agents}}
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