Identification

Name
Lumefantrine
Accession Number
DB06708
Type
Small Molecule
Groups
Approved
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)-α-((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
Product Images
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
CoartemLumefantrine (120 mg/1) + Artemether (20 mg/1)TabletOralCentral Texas Community Health Centers2009-04-07Not applicableUs
CoartemLumefantrine (120 mg/1) + Artemether (20 mg/1)TabletOralNovartis Pharmaceuticals Corporation2009-04-07Not applicableUs00078 0568 45 nlmimage10 6c443641
CoartemLumefantrine (120 mg/1) + Artemether (20 mg/1)TabletOralDepartment Of State Health Services, Pharmacy Branch2009-04-072018-02-28Us
Categories
UNII
F38R0JR742
CAS number
82186-77-4
Weight
Average: 528.94
Monoisotopic: 527.154947772
Chemical Formula
C30H32Cl3NO
InChI Key
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

Pharmacology

Indication

Lumefantrine 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.

Associated Conditions
Pharmacodynamics

Lumefantrine 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 action

The 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.

Absorption

Food increases absorption.

Volume of distribution
Not Available
Protein binding

99.7% bound

Metabolism

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

Route of elimination
Not Available
Half life

~ 4.5 days

Clearance
Not Available
Toxicity

Common 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be increased when combined with Lumefantrine.
(S)-WarfarinThe metabolism of (S)-Warfarin can be increased when combined with Lumefantrine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Lumefantrine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Lumefantrine.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Lumefantrine.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Lumefantrine.
6-Deoxyerythronolide BThe metabolism of Lumefantrine can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be increased when combined with Lumefantrine.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be increased when combined with Lumefantrine.
AbataceptThe metabolism of Lumefantrine can be increased when combined with Abatacept.
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.

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015653
KEGG Drug
D03821
PubChem Compound
6437380
PubChem Substance
99443260
ChemSpider
4941944
BindingDB
50123012
ChEBI
156095
ChEMBL
CHEMBL38827
PharmGKB
PA165111722
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Lumefantrine
ATC Codes
P01BF01 — Artemether and lumefantrine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedHealth Services ResearchHuman Immunodeficiency Virus (HIV)1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Plasmodium Infections1
1CompletedTreatmentMalaria caused by plasmodium vivax1
1Enrolling by InvitationPreventionPlasmodium Infections1
1RecruitingPreventionPlasmodium Infections1
2Active Not RecruitingTreatmentPlasmodium Infections1
2RecruitingTreatmentAcute Uncomplicated Plasmodium Falciparum Malaria1
2RecruitingTreatmentPlasmodium Infections2
2TerminatedTreatmentPlasmodium Infections1
3Active Not RecruitingTreatmentPlasmodium Infections1
3CompletedTreatmentMalaria caused by plasmodium vivax1
3CompletedTreatmentMalaria in Pregnancy1
3CompletedTreatmentPlasmodium Falciparum Infection1
3CompletedTreatmentPlasmodium Falciparum Malaria2
3CompletedTreatmentPlasmodium Infections10
3Unknown StatusTreatmentPlasmodium Infections1
4CompletedNot AvailablePlasmodium Infections1
4CompletedBasic ScienceHuman Immunodeficiency Virus (HIV) Infections1
4CompletedBasic SciencePlasmodium Falciparum Clinical Episode / Plasmodium Falciparum Infection / Plasmodium Vivax Clinical Episode / Plasmodium Vivax Infection1
4CompletedHealth Services ResearchAnemias / Plasmodium Infections / Pregnancy1
4CompletedOtherPlasmodium Infections1
4CompletedTreatmentFalciparum / Plasmodium Infections1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Plasmodium Infections1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) / Plasmodium Infections1
4CompletedTreatmentInstantaneous Clearance1
4CompletedTreatmentMalaria caused by Plasmodium falciparum4
4CompletedTreatmentParasitologically Confirmed; Malarial1
4CompletedTreatmentPlasmodium Falciparum Malaria3
4CompletedTreatmentPlasmodium Infections10
4RecruitingTreatmentUncomplicated Plasmodium Falciparum Malaria1
4TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Plasmodium Infections1
4TerminatedTreatmentMalaria caused by Plasmodium falciparum1
4TerminatedTreatmentPlasmodium Infections1
4TerminatedTreatmentPlasmodium Vivax Malaria1
4Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis Infection1
4Unknown StatusTreatmentPlasmodium Infections2
4Unknown StatusTreatmentUncomplicated Falciparum Malaria1
4Unknown StatusTreatmentUncomplicated Malaria1
Not AvailableCompletedNot AvailableUncomplicated Malaria1
Not AvailableCompletedHealth Services ResearchPlasmodium Infections / Pneumonia1
Not AvailableCompletedOtherPlasmodium Infections1
Not AvailableCompletedTreatmentMalaria caused by Plasmodium falciparum1
Not AvailableCompletedTreatmentNon-malarial Febrile Illness / Plasmodium Infections1
Not AvailableCompletedTreatmentPlasmodium Infections2
Not AvailableCompletedTreatmentPlasmodium Infections / Pneumonia1
Not AvailableCompletedTreatmentUncomplicated Malaria2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not 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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Fluorenes
Sub Class
Not Available
Direct Parent
Fluorenes
Alternative Parents
Chlorobenzenes / Aralkylamines / Aryl chlorides / Trialkylamines / Secondary alcohols / 1,2-aminoalcohols / Organopnictogen compounds / Organochlorides / Hydrocarbon derivatives / Aromatic alcohols
Substituents
Fluorene / Chlorobenzene / Aralkylamine / Halobenzene / Aryl chloride / Aryl halide / Monocyclic benzene moiety / 1,2-aminoalcohol / Tertiary aliphatic amine / Secondary alcohol
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
tertiary amine, secondary alcohol, monochlorobenzenes, fluorenes (CHEBI:156095)

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inducer
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da

Drug created on May 15, 2010 19:04 / Updated on December 14, 2018 17:11