Lumefantrine
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Identification
- Summary
Lumefantrine is an antimalarial agent used in combination with artemether for the treatment of acute uncomplicated malaria caused by Plasmodium falciparum.
- Brand Names
- Coartem
- Generic Name
- Lumefantrine
- DrugBank Accession Number
- DB06708
- Background
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.
- Type
- Small Molecule
- Groups
- Approved
- Structure
- Weight
- Average: 528.94
Monoisotopic: 527.154947772 - Chemical Formula
- C30H32Cl3NO
- 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
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.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Uncomplicated malaria caused by plasmodium falciparum Combination Product in combination with: Artemether (DB06697) •••••••••••• - Contraindications & Blackbox Warnings
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- 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.
Target Actions Organism ASodium/potassium-transporting ATPase subunit alpha-1 binderHumans - 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.
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- Route of elimination
Not Available
- Half-life
~ 4.5 days
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- 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.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Lumefantrine can be increased when it is combined with Abametapir. Acebutolol The metabolism of Acebutolol can be decreased when combined with Lumefantrine. Acetaminophen The metabolism of Acetaminophen can be decreased when combined with Lumefantrine. Acetophenazine The risk or severity of QTc prolongation can be increased when Lumefantrine is combined with Acetophenazine. Acrivastine The risk or severity of QTc prolongation can be increased when Acrivastine is combined with Lumefantrine. - Food Interactions
- Avoid grapefruit products.
- Take with food. Food increases absorption.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Images
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Coartem Lumefantrine (120 mg/1) + Artemether (20 mg/1) Tablet Oral Department Of State Health Services, Pharmacy Branch 2009-04-07 2018-02-28 US Coartem Lumefantrine (120 mg/1) + Artemether (20 mg/1) Tablet Oral Central Texas Community Health Centers 2009-04-07 Not applicable US Coartem Lumefantrine (120 mg/1) + Artemether (20 mg/1) Tablet Oral Novartis Farma S.P.A. 2009-04-07 Not applicable US COARTEM 20/120 Lumefantrine (120 mg) + Artemether (20 mg) Tablet, orally disintegrating Oral บริษัท โนวาร์ตีส (ประเทศไทย) จำกัด 2017-10-28 Not applicable Thailand COARTEM DISPERSIBLE (20/120 MG TABLETS) Lumefantrine (120 MG) + Artemether (20 MG) Tablet, soluble Oral บริษัท โนวาร์ตีส (ประเทศไทย) จำกัด 2017-10-28 Not applicable Thailand
Categories
- ATC Codes
- P01BF01 — Artemether and lumefantrine
- Drug Categories
- Anti-Infective Agents
- Antimalarials
- Antiparasitic Agents
- Antiparasitic Products, Insecticides and Repellents
- Antiprotozoals
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (moderate)
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Fluorenes
- Highest Risk QTc-Prolonging Agents
- QTc Prolonging Agents
- Chemical TaxonomyProvided by Classyfire
- 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
- 1,2-aminoalcohol / Alcohol / Amine / Aralkylamine / Aromatic alcohol / Aromatic homopolycyclic compound / Aryl chloride / Aryl halide / Chlorobenzene / Fluorene
- Molecular Framework
- Aromatic homopolycyclic compounds
- External Descriptors
- tertiary amine, secondary alcohol, monochlorobenzenes, fluorenes (CHEBI:156095)
- Affected organisms
- Plasmodium
Chemical Identifiers
- UNII
- F38R0JR742
- CAS number
- 82186-77-4
- 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
References
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015653
- KEGG Drug
- D03821
- PubChem Compound
- 6437380
- PubChem Substance
- 99443260
- ChemSpider
- 4941944
- BindingDB
- 50238630
- 847728
- ChEBI
- 156095
- ChEMBL
- CHEMBL38827
- PharmGKB
- PA165111722
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Lumefantrine
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Not Available Malaria caused by Plasmodium falciparum 1 somestatus stop reason just information to hide Not Available Completed Not Available Malaria 1 somestatus stop reason just information to hide Not Available Completed Not Available Malaria caused by Plasmodium falciparum / Malaria Recrudescence 2 somestatus stop reason just information to hide Not Available Completed Not Available Malaria / Malaria caused by Plasmodium falciparum / Malaria caused by plasmodium vivax / Malaria Recrudescence 1 somestatus stop reason just information to hide Not Available Completed Not Available Uncomplicated Malaria 2 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral Tablet, orally disintegrating Oral Tablet, soluble Oral Tablet, film coated Oral Tablet Oral 20 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 3.09e-05 mg/mL ALOGPS logP 8.34 ALOGPS logP 9.19 Chemaxon logS -7.2 ALOGPS pKa (Strongest Acidic) 14.1 Chemaxon pKa (Strongest Basic) 9.78 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 23.47 Å2 Chemaxon Rotatable Bond Count 10 Chemaxon Refractivity 160.81 m3·mol-1 Chemaxon Polarizability 60.69 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule Yes Chemaxon - 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 inhibitor Non-inhibitor 0.7112 CYP450 2D6 inhibitor Inhibitor 0.7727 CYP450 2C19 inhibitor Non-inhibitor 0.6525 CYP450 3A4 inhibitor 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 223.8673454 predictedDarkChem Lite v0.1.0 [M-H]- 222.5257 predictedDeepCCS 1.0 (2019) [M+H]+ 223.8309454 predictedDarkChem Lite v0.1.0 [M+H]+ 224.92125 predictedDeepCCS 1.0 (2019) [M+Na]+ 224.0939454 predictedDarkChem Lite v0.1.0 [M+Na]+ 230.83379 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients (PubMed:29499166, PubMed:30388404). Could also be part of an osmosensory signaling pathway that senses body-fluid sodium levels and controls salt intake behavior as well as voluntary water intake to regulate sodium homeostasis (By similarity)
- Specific Function
- ATP binding
- Gene Name
- ATP1A1
- Uniprot ID
- P05023
- Uniprot Name
- Sodium/potassium-transporting ATPase subunit alpha-1
- Molecular Weight
- 112895.01 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- FDA Approved Drug Products: COARTEM (artemether and lumefantrine) tablets, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Lumefantrine inhibits CYP2D6 in vitro.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- FDA Approved Drug Products: COARTEM (artemether and lumefantrine) tablets, for oral use [Link]
Drug created at May 16, 2010 01:04 / Updated at August 26, 2024 19:23