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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
(+-)-2,7-Dichloro-9-((Z)-P-chlorobenzylidene)-alpha-((dibutylamino)methyl)fluorene-4-methanol
2-Dibutylamino-1-[2,7-dichloro-9-(4-chloro-benzylidene)-9H-fluoren-4-yl]-ethanol
2-Dibutylamino-1-{2,7-dichloro-9-[1-(4-chloro-phenyl)-meth-(Z)-ylidene]-9H-fluoren-4-yl}-ethanol
Benflumetol
DL-Benflumelol
Lumefantrine
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameLabellerIngredients
CoartemNovartis Pharmaceuticals Corporation
SaltsNot Available
Categories
UNIIF38R0JR742
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
Taxonomy
ClassificationNot classified
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.
Related Articles
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
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9363
Caco-2 permeable+0.6319
P-glycoprotein substrateSubstrate0.8389
P-glycoprotein inhibitor IInhibitor0.6854
P-glycoprotein inhibitor IINon-inhibitor0.5475
Renal organic cation transporterInhibitor0.5792
CYP450 2C9 substrateNon-substrate0.7971
CYP450 2D6 substrateNon-substrate0.9117
CYP450 3A4 substrateSubstrate0.7076
CYP450 1A2 substrateInhibitor0.6872
CYP450 2C9 inhibitorNon-inhibitor0.7112
CYP450 2D6 inhibitorInhibitor0.7727
CYP450 2C19 inhibitorNon-inhibitor0.6525
CYP450 3A4 inhibitorNon-inhibitor0.6983
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7168
Ames testNon AMES toxic0.6424
CarcinogenicityNon-carcinogens0.7629
BiodegradationNot ready biodegradable0.9924
Rat acute toxicity2.4077 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.7654
hERG inhibition (predictor II)Inhibitor0.776
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tabletoral
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility3.09e-05 mg/mLALOGPS
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 Area23.47 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity160.81 m3·mol-1ChemAxon
Polarizability60.69 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesP01BF01
AHFS Codes
  • 8:30.08
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcepromazineThe serum concentration of Acepromazine can be increased when it is combined with Lumefantrine.
ArtesunateThe risk or severity of adverse effects can be increased when Artesunate is combined with Lumefantrine.
BexaroteneThe serum concentration of Lumefantrine can be decreased when it is combined with Bexarotene.
BoceprevirThe serum concentration of Lumefantrine can be increased when it is combined with Boceprevir.
CarbamazepineThe serum concentration of Lumefantrine can be decreased when it is combined with Carbamazepine.
ChloroquineThe risk or severity of adverse effects can be increased when Chloroquine is combined with Lumefantrine.
ChlorotrianiseneThe serum concentration of Chlorotrianisene can be decreased when it is combined with Lumefantrine.
CitalopramCitalopram may increase the QTc-prolonging activities of Lumefantrine.
CobicistatThe serum concentration of Lumefantrine can be increased when it is combined with Cobicistat.
DapsoneThe risk or severity of adverse effects can be increased when Lumefantrine is combined with Dapsone.
DarunavirThe serum concentration of Lumefantrine can be increased when it is combined with Darunavir.
DofetilideDofetilide may increase the QTc-prolonging activities of Lumefantrine.
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Lumefantrine.
EnzalutamideThe serum concentration of Lumefantrine can be decreased when it is combined with Enzalutamide.
FluvoxamineThe metabolism of Fluvoxamine can be decreased when combined with Lumefantrine.
FosphenytoinThe serum concentration of Lumefantrine can be decreased when it is combined with Fosphenytoin.
GoserelinGoserelin may increase the QTc-prolonging activities of Lumefantrine.
HydroxychloroquineThe risk or severity of adverse effects can be increased when Hydroxychloroquine is combined with Lumefantrine.
IdelalisibThe serum concentration of Lumefantrine can be increased when it is combined with Idelalisib.
IndinavirThe serum concentration of Lumefantrine can be increased when it is combined with Indinavir.
LeuprolideLeuprolide may increase the QTc-prolonging activities of Lumefantrine.
MefloquineThe risk or severity of adverse effects can be increased when Mefloquine is combined with Lumefantrine.
MitotaneThe serum concentration of Lumefantrine can be decreased when it is combined with Mitotane.
NefazodoneThe serum concentration of Lumefantrine can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Lumefantrine can be increased when it is combined with Nelfinavir.
NorethisteroneThe serum concentration of Norethindrone can be decreased when it is combined with Lumefantrine.
OctreotideOctreotide may increase the QTc-prolonging activities of Lumefantrine.
PhenobarbitalThe serum concentration of Lumefantrine can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Lumefantrine can be decreased when it is combined with Phenytoin.
PrimaquineThe risk or severity of adverse effects can be increased when Primaquine is combined with Lumefantrine.
PrimidoneThe serum concentration of Lumefantrine can be decreased when it is combined with Primidone.
PyrimethamineThe risk or severity of adverse effects can be increased when Pyrimethamine is combined with Lumefantrine.
QuinineThe risk or severity of adverse effects can be increased when Quinine is combined with Lumefantrine.
RifabutinThe serum concentration of Lumefantrine can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Lumefantrine can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Lumefantrine can be decreased when it is combined with Rifapentine.
St. John's WortThe serum concentration of the active metabolites of Lumefantrine can be reduced when Lumefantrine is used in combination with St. John's Wort resulting in a loss in efficacy.
TelaprevirThe serum concentration of Lumefantrine can be increased when it is combined with Telaprevir.
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.

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
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
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
Comments
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Drug created on May 15, 2010 19:04 / Updated on August 17, 2016 12:24