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Identification
NameLomitapide
Accession NumberDB08827
TypeSmall Molecule
GroupsApproved
Description

Lomitapide is a microsomal triglyceride transfer protein (MTP) inhibitor used in homozygous familial hypercholesterolemia (HoFH) patients. It is marketed under the name Juxtapid®.

Structure
Thumb
Synonyms
AEGR 733
BMS 201038
External Identifiers
  • AEGR-773
  • BMS 201038
  • BMS-201038-04
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Juxtapidcapsule5 mg/1oralAegerion Pharmaceuticals, Inc.2013-01-03Not applicableUs
Juxtapidcapsule5 mgoralAegerion Pharmaceuticals Canada Ltd2014-05-06Not applicableCanada
Juxtapidcapsule60 mg/1oralAegerion Pharmaceuticals, Inc.2013-01-03Not applicableUs
Juxtapidcapsule40 mg/1oralAegerion Pharmaceuticals, Inc.2013-01-03Not applicableUs
Juxtapidcapsule30 mg/1oralAegerion Pharmaceuticals, Inc.2013-01-03Not applicableUs
Juxtapidcapsule20 mg/1oralAegerion Pharmaceuticals, Inc.2013-01-03Not applicableUs
Juxtapidcapsule20 mgoralAegerion Pharmaceuticals Canada Ltd2014-05-06Not applicableCanada
Juxtapidcapsule10 mg/1oralAegerion Pharmaceuticals, Inc.2013-01-03Not applicableUs
Juxtapidcapsule10 mgoralAegerion Pharmaceuticals Canada Ltd2014-05-06Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
LojuxtaNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Lomitapide mesylate
202914-84-9
Thumb
  • InChI Key: QKVKOFVWUHNEBX-UHFFFAOYSA-N
  • Monoisotopic Mass: 789.267111357
  • Average Mass: 789.826
DBSALT000110
Categories
UNII82KUB0583F
CAS number182431-12-5
WeightAverage: 693.7204
Monoisotopic: 693.278996673
Chemical FormulaC39H37F6N3O2
InChI KeyInChIKey=MBBCVAKAJPKAKM-UHFFFAOYSA-N
InChI
InChI=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)
IUPAC Name
N-(2,2,2-trifluoroethyl)-9-[4-(4-{2-[4-(trifluoromethyl)phenyl]benzamido}piperidin-1-yl)butyl]-9H-fluorene-9-carboxamide
SMILES
FC(F)(F)CNC(=O)C1(CCCCN2CCC(CC2)NC(=O)C2=C(C=CC=C2)C2=CC=C(C=C2)C(F)(F)F)C2=CC=CC=C2C2=CC=CC=C12
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as fluorenes. These are compounds containing a fluorene moiety, which consists of two benzene rings connected through either a cyclopentane, cyclopentene, or cyclopenta-1,3-diene.
KingdomOrganic compounds
Super ClassBenzenoids
ClassFluorenes
Sub ClassNot Available
Direct ParentFluorenes
Alternative Parents
Substituents
  • Fluorene
  • Biphenyl
  • Benzoic acid or derivatives
  • Benzamide
  • Benzoyl
  • Aralkylamine
  • 4-aminopiperidine
  • Fatty acyl
  • Piperidine
  • Fatty amide
  • Monocyclic benzene moiety
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Alkyl halide
  • Alkyl fluoride
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationUsed in homozygous familial hypercholesterolemia (HoFH) patients to reduce low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), apolipoprotein B (apo B), and non-high-density lipoprotein cholesterol (non-HDL-C).
PharmacodynamicsLomitapide directly inhibits microsomal triglyceride transfer protein (MTP).
Mechanism of actionWithin the lumen of the endoplasmic reticulum, lomitapide inhibits microsomal triglyceride transfer protein (MTP), which prevents the formation of apolipoprotein B, and, thus, the formation of VLDL and chylomicrons as well. Altogether, this leads to a reduction of low-density lipoprotein cholesterol.
Related Articles
AbsorptionIn healthy patients, time to maximum lomitapide concentration is about 6 hours with a single dose of 60 mg. Lomitapide has an approximate absolute bioavailability of 7%.
Volume of distribution

The steady state volume of distribution is about 985-1292 L.

Protein bindingPlasma protein binding is about 99.8%
Metabolism

Lomitapide is mainly metabolized by CYP3A4 to it's inactive metabolites, M1 and M3. CYP enzymes that metabolize lomitapide to a minor extent include CYP 1A2,2B6,2C8,2C19.

Route of eliminationAbout 52.9-59.5% is eliminated by the urine and 33.4-35.1% is eliminated by the feces.
Half lifeLomitapide half-life is about 39.7 hours.
ClearanceNot Available
ToxicityContra-indicated in pregnancy, and moderate to severe hepatic insufficiency (Child-Pugh category B or C). Severe GI adverse reactions may occur.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal AbsorptionNot AvailableNot Available
Blood Brain BarrierNot AvailableNot Available
Caco-2 permeableNot AvailableNot Available
P-glycoprotein substrateNot AvailableNot Available
P-glycoprotein inhibitor INot AvailableNot Available
P-glycoprotein inhibitor IINot AvailableNot Available
Renal organic cation transporterNot AvailableNot Available
CYP450 2C9 substrateNot AvailableNot Available
CYP450 2D6 substrateNot AvailableNot Available
CYP450 3A4 substrateNot AvailableNot Available
CYP450 1A2 substrateNot AvailableNot Available
CYP450 2C9 inhibitorNot AvailableNot Available
CYP450 2D6 inhibitorNot AvailableNot Available
CYP450 2C19 inhibitorNot AvailableNot Available
CYP450 3A4 inhibitorNot AvailableNot Available
CYP450 inhibitory promiscuityNot AvailableNot Available
Ames testNot AvailableNot Available
CarcinogenicityNot AvailableNot Available
BiodegradationNot AvailableNot Available
Rat acute toxicityNot AvailableNot applicable
hERG inhibition (predictor I)Not AvailableNot Available
hERG inhibition (predictor II)Not AvailableNot Available
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Capsuleoral10 mg
Capsuleoral10 mg/1
Capsuleoral20 mg/1
Capsuleoral20 mg
Capsuleoral30 mg/1
Capsuleoral40 mg/1
Capsuleoral5 mg/1
Capsuleoral5 mg
Capsuleoral60 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5712279 No1996-02-212016-02-21Us
US5739135 No2012-12-122015-04-14Us
US6492365 No1999-12-102019-12-10Us
US7932268 No2007-08-192027-08-19Us
US8618135 No2005-03-072025-03-07Us
US9265758 No2005-03-072025-03-07Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
logP7.7ChemAxon
pKa (Strongest Acidic)10.35ChemAxon
pKa (Strongest Basic)9.02ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area61.44 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity181.73 m3·mol-1ChemAxon
Polarizability68.08 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Cuchel M, Meagher EA, du Toit Theron H, Blom DJ, Marais AD, Hegele RA, Averna MR, Sirtori CR, Shah PK, Gaudet D, Stefanutti C, Vigna GB, Du Plessis AM, Propert KJ, Sasiela WJ, Bloedon LT, Rader DJ: Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. Lancet. 2013 Jan 5;381(9860):40-6. doi: 10.1016/S0140-6736(12)61731-0. Epub 2012 Nov 2. [PubMed:23122768 ]
  2. Cuchel M, Bloedon LT, Szapary PO, Kolansky DM, Wolfe ML, Sarkis A, Millar JS, Ikewaki K, Siegelman ES, Gregg RE, Rader DJ: Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med. 2007 Jan 11;356(2):148-56. [PubMed:17215532 ]
External Links
ATC CodesC10AX12
AHFS Codes
  • 24:06.92
PDB EntriesNot Available
FDA labelDownload (930 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Lomitapide.
AlprazolamThe serum concentration of Lomitapide can be increased when it is combined with Alprazolam.
AmiodaroneThe serum concentration of Lomitapide can be increased when it is combined with Amiodarone.
AmlodipineThe serum concentration of Lomitapide can be increased when it is combined with Amlodipine.
AprepitantThe serum concentration of Lomitapide can be increased when it is combined with Aprepitant.
AripiprazoleThe serum concentration of Aripiprazole can be increased when it is combined with Lomitapide.
AtazanavirThe serum concentration of Lomitapide can be increased when it is combined with Atazanavir.
AtorvastatinThe serum concentration of Lomitapide can be increased when it is combined with Atorvastatin.
BexaroteneThe serum concentration of Lomitapide can be decreased when it is combined with Bexarotene.
BicalutamideThe serum concentration of Lomitapide can be increased when it is combined with Bicalutamide.
BoceprevirThe serum concentration of Lomitapide can be increased when it is combined with Boceprevir.
BosentanThe serum concentration of Lomitapide can be decreased when it is combined with Bosentan.
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Lomitapide.
Brentuximab vedotinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Lomitapide.
CeritinibThe serum concentration of Lomitapide can be increased when it is combined with Ceritinib.
CholestyramineCholestyramine can cause a decrease in the absorption of Lomitapide resulting in a reduced serum concentration and potentially a decrease in efficacy.
CilostazolThe serum concentration of Lomitapide can be increased when it is combined with Cilostazol.
CimetidineThe serum concentration of Lomitapide can be increased when it is combined with Cimetidine.
CiprofloxacinThe serum concentration of Lomitapide can be increased when it is combined with Ciprofloxacin.
ClarithromycinThe serum concentration of Lomitapide can be increased when it is combined with Clarithromycin.
ClotrimazoleThe serum concentration of Lomitapide can be increased when it is combined with Clotrimazole.
CobicistatThe serum concentration of Lomitapide can be increased when it is combined with Cobicistat.
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Lomitapide.
ColesevelamColesevelam can cause a decrease in the absorption of Lomitapide resulting in a reduced serum concentration and potentially a decrease in efficacy.
ColestipolColestipol can cause a decrease in the absorption of Lomitapide resulting in a reduced serum concentration and potentially a decrease in efficacy.
ConivaptanThe serum concentration of Lomitapide can be increased when it is combined with Conivaptan.
CrizotinibThe serum concentration of Lomitapide can be increased when it is combined with Crizotinib.
CyclosporineThe serum concentration of Lomitapide can be increased when it is combined with Cyclosporine.
Dabigatran etexilateThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Lomitapide.
DabrafenibThe serum concentration of Lomitapide can be decreased when it is combined with Dabrafenib.
DanazolThe serum concentration of Lomitapide can be increased when it is combined with Danazol.
DarunavirThe serum concentration of Lomitapide can be increased when it is combined with Darunavir.
DasatinibThe serum concentration of Lomitapide can be increased when it is combined with Dasatinib.
DeferasiroxThe serum concentration of Lomitapide can be decreased when it is combined with Deferasirox.
DelavirdineThe serum concentration of Lomitapide can be increased when it is combined with Delavirdine.
DiltiazemThe serum concentration of Lomitapide can be increased when it is combined with Diltiazem.
DofetilideThe serum concentration of Dofetilide can be increased when it is combined with Lomitapide.
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Lomitapide.
DronedaroneThe serum concentration of Lomitapide can be increased when it is combined with Dronedarone.
EdoxabanThe serum concentration of Edoxaban can be increased when it is combined with Lomitapide.
ErythromycinThe serum concentration of Lomitapide can be increased when it is combined with Erythromycin.
EthanolEthanol may increase the hepatotoxic activities of Lomitapide.
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Lomitapide.
FlibanserinThe serum concentration of Flibanserin can be increased when it is combined with Lomitapide.
FluconazoleThe serum concentration of Lomitapide can be increased when it is combined with Fluconazole.
FluvoxamineThe serum concentration of Lomitapide can be increased when it is combined with Fluvoxamine.
FosamprenavirThe serum concentration of Lomitapide can be increased when it is combined with Fosamprenavir.
FosaprepitantThe serum concentration of Lomitapide can be increased when it is combined with Fosaprepitant.
Fusidic AcidThe serum concentration of Lomitapide can be increased when it is combined with Fusidic Acid.
Glycerol PhenylbutyrateThe serum concentration of Lomitapide can be increased when it is combined with Glycerol Phenylbutyrate.
HydrocodoneThe serum concentration of Hydrocodone can be increased when it is combined with Lomitapide.
IdelalisibThe serum concentration of Lomitapide can be increased when it is combined with Idelalisib.
IloperidoneThe serum concentration of Lomitapide can be increased when it is combined with Iloperidone.
ImatinibThe serum concentration of Lomitapide can be increased when it is combined with Imatinib.
IndinavirThe serum concentration of Lomitapide can be increased when it is combined with Indinavir.
IsavuconazoniumThe serum concentration of Lomitapide can be increased when it is combined with Isavuconazonium.
IsoniazidThe serum concentration of Lomitapide can be increased when it is combined with Isoniazid.
ItraconazoleThe serum concentration of Lomitapide can be increased when it is combined with Itraconazole.
IvacaftorThe serum concentration of Lomitapide can be increased when it is combined with Ivacaftor.
KetoconazoleThe serum concentration of Lomitapide can be increased when it is combined with Ketoconazole.
LapatinibThe serum concentration of Lomitapide can be increased when it is combined with Lapatinib.
LedipasvirThe serum concentration of Ledipasvir can be increased when it is combined with Lomitapide.
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Lomitapide.
LuliconazoleThe serum concentration of Lomitapide can be increased when it is combined with Luliconazole.
LurasidoneThe serum concentration of Lomitapide can be increased when it is combined with Lurasidone.
MifepristoneThe serum concentration of Lomitapide can be increased when it is combined with Mifepristone.
MipomersenLomitapide may increase the hepatotoxic activities of Mipomersen.
MitotaneThe serum concentration of Lomitapide can be decreased when it is combined with Mitotane.
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Lomitapide.
NefazodoneThe serum concentration of Lomitapide can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Lomitapide can be increased when it is combined with Nelfinavir.
NicardipineThe serum concentration of Lomitapide can be increased when it is combined with Nicardipine.
NilotinibThe serum concentration of Lomitapide can be increased when it is combined with Nilotinib.
NimodipineThe serum concentration of Nimodipine can be increased when it is combined with Lomitapide.
PalbociclibThe serum concentration of Lomitapide can be increased when it is combined with Palbociclib.
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Lomitapide.
PhenytoinThe metabolism of Lomitapide can be increased when combined with Phenytoin.
PimozideThe serum concentration of Pimozide can be increased when it is combined with Lomitapide.
PosaconazoleThe serum concentration of Lomitapide can be increased when it is combined with Posaconazole.
PropofolThe serum concentration of Lomitapide can be increased when it is combined with Propofol.
PrucaloprideThe serum concentration of Prucalopride can be increased when it is combined with Lomitapide.
QuinidineThe serum concentration of Lomitapide can be increased when it is combined with Quinidine.
RanolazineThe serum concentration of Lomitapide can be increased when it is combined with Ranolazine.
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Lomitapide.
RitonavirThe serum concentration of Lomitapide can be increased when it is combined with Ritonavir.
SaquinavirThe serum concentration of Lomitapide can be increased when it is combined with Saquinavir.
SilodosinThe serum concentration of Silodosin can be increased when it is combined with Lomitapide.
SiltuximabThe serum concentration of Lomitapide can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Lomitapide can be increased when it is combined with Simeprevir.
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Lomitapide.
St. John's WortThe serum concentration of Lomitapide can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Lomitapide can be increased when it is combined with Stiripentol.
TelaprevirThe serum concentration of Lomitapide can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Lomitapide can be increased when it is combined with Telithromycin.
TicagrelorThe serum concentration of Lomitapide can be increased when it is combined with Ticagrelor.
TiclopidineThe serum concentration of Lomitapide can be increased when it is combined with Ticlopidine.
TipranavirThe serum concentration of Lomitapide can be increased when it is combined with Tipranavir.
TocilizumabThe serum concentration of Lomitapide can be decreased when it is combined with Tocilizumab.
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Lomitapide.
VerapamilThe serum concentration of Lomitapide can be increased when it is combined with Verapamil.
VincristineThe serum concentration of Vincristine can be increased when it is combined with Lomitapide.
VoriconazoleThe serum concentration of Lomitapide can be increased when it is combined with Voriconazole.
WarfarinThe serum concentration of Warfarin can be increased when it is combined with Lomitapide.
Food Interactions
  • Avoid grapefruit juice, which will likely increase lomitapide plasma concentrations.
  • When taking lomitapide with food, the risk of GI side effects is increased.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Protein heterodimerization activity
Specific Function:
Catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces (PubMed:23475612, PubMed:8939939, PubMed:26224785, PubMed:25108285, PubMed:22236406). Required for the secretion of plasma lipoproteins that contain apolipoprotein B (PubMed:23475612, PubMed:8939939, PubMed:26224785).
Gene Name:
MTTP
Uniprot ID:
P55157
Molecular Weight:
99350.255 Da

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
no
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
no
Actions
inhibitor
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
Comments
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Drug created on January 03, 2013 13:34 / Updated on August 24, 2016 02:00