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Identification
NameLumefantrine
Accession NumberDB06708
Typesmall molecule
Groupsapproved
Description

Lumefantrine is an antimalarial agent used to treat acute uncomplicated malaria. It is administered in combination with artemether for improved efficacy. This combination therapy exerts its effects against the erythrocytic stages of Plasmodium spp. and may be used to treat infections caused by P. falciparum and unidentified Plasmodium species, including infections acquired in chloroquine-resistant areas.

Structure
Thumb
Synonyms
SynonymLanguageCode
BenflumetolNot AvailableNot Available
SaltsNot Available
Brand namesNot Available
Brand mixtures
Brand NameIngredients
CoartemArtemether + Lumefantrine
Categories
CAS number82186-77-4
WeightAverage: 528.94
Monoisotopic: 527.154947772
Chemical FormulaC30H32Cl3NO
InChI KeyInChIKey=DYLGFOYVTXJFJP-MYYYXRDXSA-N
InChI
InChI=1S/C30H32Cl3NO/c1-3-5-13-34(14-6-4-2)19-29(35)28-18-23(33)17-27-25(15-20-7-9-21(31)10-8-20)26-16-22(32)11-12-24(26)30(27)28/h7-12,15-18,29,35H,3-6,13-14,19H2,1-2H3/b25-15-
IUPAC Name
2-(dibutylamino)-1-[(9Z)-2,7-dichloro-9-[(4-chlorophenyl)methylidene]-9H-fluoren-4-yl]ethan-1-ol
SMILES
CCCCN(CCCC)CC(O)C1=C2C(=CC(Cl)=C1)\C(=C/C1=CC=C(Cl)C=C1)C1=C2C=CC(Cl)=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassPhenylpropanoids and Polyketides
ClassStilbenes
SubclassNot Available
Direct parentStilbenes
Alternative parentsFluorenes; Chlorobenzenes; Aryl Chlorides; Tertiary Amines; Secondary Alcohols; Polyamines; Organochlorides
Substituentschlorobenzene; aryl halide; aryl chloride; benzene; secondary alcohol; tertiary amine; polyamine; organohalogen; organochloride; amine; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
Pharmacology
IndicationLumefantrine and artemether combination therapy is indicated for the treatment of acute uncomplicated malaria caused by Plasmodium falciparum, including malaria acquired in chloroquine-resistant areas. May also be used to treat uncomplicated malaria when the Plasmodium species has not been identified. Indicated for use in adults and children greater than 5 kg.
PharmacodynamicsLumefantrine is a blood schizonticide active against erythrocytic stages of Plasmodium falciparum. It is thought that administration of lumefantrine with artemether results in cooperate antimalarial clearing effects. Artemether has a rapid onset of action and is rapidly cleared from the body. It is thus thought to provide rapid symptomatic relief by reducing the number of malarial parasites. Lumefantrine has a much longer half life and is believed to clear residual parasites.
Mechanism of actionThe exact mechanism by which lumefantrine exerts its antimalarial effect is unknown. However, available data suggest that lumefantrine inhibits the formation of β-hematin by forming a complex with hemin and inhibits nucleic acid and protein synthesis.
AbsorptionFood increases absorption.
Volume of distributionNot Available
Protein binding99.7% bound
Metabolism

Extensively metabolized in the liver primarily by cytochrome P450 3A4. The major metabolite found in plasma is desbutyl-lumefantrine.

SubstrateEnzymesProduct
Lumefantrine
desbutyl-lumefantrineDetails
Route of eliminationNot Available
Half life~ 4.5 days
ClearanceNot Available
ToxicityCommon side effects of combination artemether/lumefantrine therapy in adults include headache, anorexia, dizziness, and asthenia. Common side effects in children include pyrexia, cough, vomiting, anorexia, and headache. Possible serious adverse effects include QT prolongation, bullous eruption, urticaria, splenomegaly (9%), hepatomegaly (adults, 9%; children, 6%), hypersensitivty reaction, and angioedema.
Affected organisms
  • Plasmodium
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9363
Caco-2 permeable + 0.6319
P-glycoprotein substrate Substrate 0.8389
P-glycoprotein inhibitor I Inhibitor 0.6854
P-glycoprotein inhibitor II Non-inhibitor 0.5475
Renal organic cation transporter Inhibitor 0.5792
CYP450 2C9 substrate Non-substrate 0.7971
CYP450 2D6 substrate Non-substrate 0.9117
CYP450 3A4 substrate Substrate 0.7076
CYP450 1A2 substrate Inhibitor 0.6872
CYP450 2C9 substrate Non-inhibitor 0.7112
CYP450 2D6 substrate Inhibitor 0.7727
CYP450 2C19 substrate Non-inhibitor 0.6525
CYP450 3A4 substrate Non-inhibitor 0.6983
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7168
Ames test Non AMES toxic 0.6424
Carcinogenicity Non-carcinogens 0.7629
Biodegradation Not ready biodegradable 0.9924
Rat acute toxicity 2.4077 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Strong inhibitor 0.7654
hERG inhibition (predictor II) Inhibitor 0.776
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral20 mg artemether and 120 mg lumefantrine
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
water solubility3.09e-05 g/lALOGPS
logP8.34ALOGPS
logP9.19ChemAxon
logS-7.2ALOGPS
pKa (strongest acidic)14.1ChemAxon
pKa (strongest basic)9.78ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count1ChemAxon
polar surface area23.47ChemAxon
rotatable bond count10ChemAxon
refractivity160.81ChemAxon
polarizability60.69ChemAxon
number of rings4ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Artemether and Lumefantrine (2010). AHFS Drug Information [Electronic versionb]. Retrieved October 24, 2010.
  2. Artemether/Lumefantrine (2010). DrugPoints® System [Electronic version]. Retrieved October 24, 2010.
  3. Novartis. Coartem (artemether/lumefantrine) tablets prescribing information. East Hanover, NJ; 2010 Feb.
External Links
ResourceLink
KEGG DrugD03821
PubChem Compound6437380
PubChem Substance99443260
BindingDB50123012
ChEBI156095
ChEMBLCHEMBL422330
PharmGKBPA165111722
RxListhttp://www.rxlist.com/coartem-drug.htm
Drugs.comhttp://www.drugs.com/pro/coartem.html
WikipediaLumefantrine
ATC CodesP01BF01
AHFS Codes
  • 8:30.08
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AmiodaroneAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
AmitriptylineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
AmoxapineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
ApomorphineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
Arsenic trioxideAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
AsenapineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
AzithromycinAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
BepridilAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
ChloroquineChloroquine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.
ChlorpromazineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
CisaprideAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
CitalopramAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
DapsoneConcomitant therapy may increase the risk of adverse hemolytic reactions. Monitor patients closely for symptoms of hemolytic reactions during concomitant therapy. Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, methoglobulin reductase deficiency or hemoglobin M are at higher risk of experiencing hemolytic reactions.
DoxepinAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
DronedaroneAdditive QTc-prolongation may occur. Concomitant therapy is contraindicated.
DroperidolAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
ErythromycinAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
EscitalopramAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
FlecainideAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
FluconazoleAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
FluoxetineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
FlupentixolAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
FoscarnetAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
GadobutrolAdditive QTc-prolongation may occur. Consider alternate therapy or monitor closely for QTc-prolongation.
Gadofosveset trisodiumAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
HalofantrineHalofantrine may increase the adverse effects of lumefantrine. Additive QTc-prolongation may occur. Combination therapy is contraindicated and therapies should not be administered within one month of each other due to the long half-life of lumefantrine.
HaloperidolAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
HydroxychloroquineHydroxychloroquine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.
IbutilideAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
IloperidoneAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
ImipramineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
IndapamideAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
IsradipineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
LapatinibAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
LevofloxacinAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
LoxapineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
MaprotilineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
MefloquineMefloquine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.
MesoridazineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
MethadoneAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
MethotrimeprazineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
MoxifloxacinAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
NilotinibAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
NorfloxacinAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
NortriptylineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
OctreotideAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
PazopanibAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
PentamidineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
PerflutrenAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
PimozideAdditive QTc-prolongation may occur. Concomitant therapy is contraindicated.
PrimaquinePrimaquine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.
ProbucolAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
ProcainamideAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
ProguanilProguanil may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.
PropafenoneAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
ProtriptylineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
PyrimethaminePyrimethamine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.
QuetiapineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
QuinidineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
QuinineQuinine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.
RanolazineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
RisperidoneAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
RomidepsinAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
SotalolAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
SparfloxacinAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
SunitinibAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
TacrolimusAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
TamoxifenLumefantrine, a moderate CYP2D6 inhibitor, may decrease the formation of highly potent tamoxifen metabolites. Concomitant therapy may decrease the effectiveness of tamoxifen. Consider alternate therapy.
TelavancinAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
TelithromycinAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
TetrabenazineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
ThioridazineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
ThiothixeneAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
ToremifeneAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
TrimipramineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
VoriconazoleAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
VorinostatAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
ZiprasidoneAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
ZuclopenthixolAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
Zuclopenthixol acetateAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
Zuclopenthixol decanoateAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
Food Interactions
  • Grapefruit juice may increase the toxicity of artemether and lumefantrine by inhibiting their metabolism.
  • Take with food as food increases the absorption of lumefantrine and artemether.

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Novartis. Coartem (artemether/lumefantrine) tablets prescribing information. East Hanover, NJ; 2010 Feb.

2. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Novartis. Coartem (artemether/lumefantrine) tablets prescribing information. East Hanover, NJ; 2010 Feb.

Comments
Drug created on May 15, 2010 19:04 / Updated on September 16, 2013 18:04