U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C30H32Cl3NO
Molecular Weight 528.9411
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of LUMEFANTRINE

SMILES

CCCCN(CCCC)CC(c1cc(cc2/C(=C(/[H])\c3ccc(cc3)Cl)/c4cc(ccc4-c21)Cl)Cl)O

InChI

InChIKey=DYLGFOYVTXJFJP-MYYYXRDXSA-N
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-

HIDE SMILES / InChI

Molecular Formula C30H32Cl3NO
Molecular Weight 528.9411
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 1
Optical Activity ( + / - )

Description
Curator's Comment:: description was created based on several sources, including: http://www.drugbank.ca/drugs/DB06708 https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7866ec19-dfac-47d4-a53f-511a12643cbf

Lumefantrine is an antimalarial agent used to treat acute uncomplicated malaria. It is administered in combination with artemether for improved efficacy (Coartem tablets). Lumefantrine is a blood schizonticide active against erythrocytic stages of Plasmodium falciparum. The exact mechanism by which lumefantrine exerts its antimalarial effect is unknown. The most common adverse reactions of Coartem in adults are headache, anorexia, dizziness, asthenia, arthralgia and myalgia.

Originator

Curator's Comment:: http://www.ncbi.nlm.nih.gov/pubmed/24650735

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
COARTEM

Approved Use

Coartem (artemether/lumefantrine) Tablets are indicated for treatment of acute, uncomplicated malaria infections due to Plasmodium falciparum in patients of 5 kg bodyweight and above. Coartem Tablets have been shown to be effective in geographical regions where resistance to chloroquine has been reported [see Clinical Studies (14.1)

Launch Date

1.23906241E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
6.2 μg/mL
480 mg 1 times / day multiple, oral
dose: 480 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LUMEFANTRINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
356 ng × h/mL
480 mg 1 times / day multiple, oral
dose: 480 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LUMEFANTRINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
6.1 h
480 mg 1 times / day multiple, oral
dose: 480 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LUMEFANTRINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.3%
480 mg 1 times / day multiple, oral
dose: 480 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LUMEFANTRINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
240 mg 3 times / day multiple, oral
Recommended
Dose: 240 mg, 3 times / day
Route: oral
Route: multiple
Dose: 240 mg, 3 times / day
Co-administed with::
artemether(40 mg; PO; 4D1+2D2)
Sources: Page: A2403
unhealthy, 2
n = 310
Health Status: unhealthy
Condition: malaria
Age Group: 2
Sex: M+F
Population Size: 310
Sources: Page: A2403
Disc. AE: Urticaria...
AEs leading to
discontinuation/dose reduction:
Urticaria (grade 3-4)
Sources: Page: A2403
480 mg 3 times / day multiple, oral
Recommended
Dose: 480 mg, 3 times / day
Route: oral
Route: multiple
Dose: 480 mg, 3 times / day
Co-administed with::
artemether(80 mg; PO; 4D1+2D2)
Sources: Page: A028
unhealthy, 25
n = 115
Health Status: unhealthy
Condition: malaria
Age Group: 25
Sex: M+F
Population Size: 115
Sources: Page: A028
Disc. AE: Abdominal pain...
Other AEs: Dyspnea, Pulmonary edema...
AEs leading to
discontinuation/dose reduction:
Abdominal pain (grade 1-2, uncommon)
Other AEs:
Dyspnea (grade 3-4, uncommon)
Pulmonary edema (grade 3-4, uncommon)
Sources: Page: A028
240 mg 3 times / day multiple, oral
Recommended
Dose: 240 mg, 3 times / day
Route: oral
Route: multiple
Dose: 240 mg, 3 times / day
Co-administed with::
artemether(40 mg; PO; 4D1+2D2)
Sources: Page: B2303
unhealthy, 3
n = 447
Health Status: unhealthy
Condition: malaria
Age Group: 3
Sex: M+F
Population Size: 447
Sources: Page: B2303
Disc. AE: Vomiting, Urticaria...
AEs leading to
discontinuation/dose reduction:
Vomiting (grade 3-4, most common)
Urticaria (grade 3-4)
Sources: Page: B2303
AEs

AEs

AESignificanceDosePopulation
Urticaria grade 3-4
Disc. AE
240 mg 3 times / day multiple, oral
Recommended
Dose: 240 mg, 3 times / day
Route: oral
Route: multiple
Dose: 240 mg, 3 times / day
Co-administed with::
artemether(40 mg; PO; 4D1+2D2)
Sources: Page: A2403
unhealthy, 2
n = 310
Health Status: unhealthy
Condition: malaria
Age Group: 2
Sex: M+F
Population Size: 310
Sources: Page: A2403
Abdominal pain grade 1-2, uncommon
Disc. AE
480 mg 3 times / day multiple, oral
Recommended
Dose: 480 mg, 3 times / day
Route: oral
Route: multiple
Dose: 480 mg, 3 times / day
Co-administed with::
artemether(80 mg; PO; 4D1+2D2)
Sources: Page: A028
unhealthy, 25
n = 115
Health Status: unhealthy
Condition: malaria
Age Group: 25
Sex: M+F
Population Size: 115
Sources: Page: A028
Dyspnea grade 3-4, uncommon
480 mg 3 times / day multiple, oral
Recommended
Dose: 480 mg, 3 times / day
Route: oral
Route: multiple
Dose: 480 mg, 3 times / day
Co-administed with::
artemether(80 mg; PO; 4D1+2D2)
Sources: Page: A028
unhealthy, 25
n = 115
Health Status: unhealthy
Condition: malaria
Age Group: 25
Sex: M+F
Population Size: 115
Sources: Page: A028
Pulmonary edema grade 3-4, uncommon
480 mg 3 times / day multiple, oral
Recommended
Dose: 480 mg, 3 times / day
Route: oral
Route: multiple
Dose: 480 mg, 3 times / day
Co-administed with::
artemether(80 mg; PO; 4D1+2D2)
Sources: Page: A028
unhealthy, 25
n = 115
Health Status: unhealthy
Condition: malaria
Age Group: 25
Sex: M+F
Population Size: 115
Sources: Page: A028
Vomiting grade 3-4, most common
Disc. AE
240 mg 3 times / day multiple, oral
Recommended
Dose: 240 mg, 3 times / day
Route: oral
Route: multiple
Dose: 240 mg, 3 times / day
Co-administed with::
artemether(40 mg; PO; 4D1+2D2)
Sources: Page: B2303
unhealthy, 3
n = 447
Health Status: unhealthy
Condition: malaria
Age Group: 3
Sex: M+F
Population Size: 447
Sources: Page: B2303
Urticaria grade 3-4
Disc. AE
240 mg 3 times / day multiple, oral
Recommended
Dose: 240 mg, 3 times / day
Route: oral
Route: multiple
Dose: 240 mg, 3 times / day
Co-administed with::
artemether(40 mg; PO; 4D1+2D2)
Sources: Page: B2303
unhealthy, 3
n = 447
Health Status: unhealthy
Condition: malaria
Age Group: 3
Sex: M+F
Population Size: 447
Sources: Page: B2303
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [IC50 >2.0 uM]
no [IC50 >2.0 uM]
no [IC50 >2.0 uM]
no [IC50 >2.0 uM]
no [IC50 >2.0 uM]
no [IC50 >2.0 uM]
no [IC50 >2.0 uM]
no
no
no
no
no
no
no
yes [IC50 0.997 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: Human liver microsomes, Recombinant CYP3A4; Modest changes (<2.5-fold increase) in systemic exposure were observed with inhibitors or substrates of CYP3A4 including ketoconazole, mefloquine or quinine. The concentrations seen in the ketoconazole drug interaction study were within the range of systemic concentrations of Coartem seen in malaria patients in Phase III efficacy and safety studies. The concurrent oral administration of ketoconazole (400 mg on Day 1 followed by 200 mg on days 2,3, 4 and 5) with co-artemether (single dose of 4 tablets of 20 mg artemether/120 mg lumefantrine) led to a modest increase in lumefantrine (1.3-fold (Cmax), 1.6-fold (AUClast)) exposure in healthy subjects.
Page: (ClinPharm) 7, 9, 11, 21, (PMDA_K100_1 in Japanese) 61
Tox targets
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Antimalarial drugs: QT prolongation and cardiac arrhythmias.
2005 May
In vitro sensitivities of Plasmodium falciparum to different antimalarial drugs in Uganda.
2010 Mar
In vitro activity of antiretroviral drugs against Plasmodium falciparum.
2011 Nov
Synthesis of novel 6-phenyl-2,4-disubstituted pyrimidine-5-carbonitriles as potential antimicrobial agents.
2011 Sep
A SYBR Green 1-based in vitro test of susceptibility of Ghanaian Plasmodium falciparum clinical isolates to a panel of anti-malarial drugs.
2013 Dec 17
Ex vivo responses of Plasmodium falciparum clinical isolates to conventional and new antimalarial drugs in Niger.
2013 Jul
Synthesis and antimalarial efficacy of two-carbon-linked, artemisinin-derived trioxane dimers in combination with known antimalarial drugs.
2013 Mar 28
Breakdown of phosphatidylserine asymmetry following treatment of erythrocytes with lumefantrine.
2014 Feb 20
In vitro and in vivo combination of cepharanthine with anti-malarial drugs.
2014 Mar 12
Patents

Sample Use Guides

Tablets should be administered over 3 days for a total of 6 doses: an initial dose, second dose after 8 hours and then twice-daily (morning and evening) for the following 2 days. The adult dosage for patients with bodyweight of 35 kg and above is 4 tablets per dose for a total of 6 doses. Tablets are scored and contain 20 mg rtemether and 120 mg lumefantrine.
Route of Administration: Oral
In Vitro Use Guide
IC90 is higher in Plasmodium falciparum strain T-996 compared with strain LS-21: for Lumefantrine 293.03 and 95.61 nmol/L (154.69 and 50.47 ng/ml of EMM).
Substance Class Chemical
Created
by admin
on Sat Jun 26 13:49:03 UTC 2021
Edited
by admin
on Sat Jun 26 13:49:03 UTC 2021
Record UNII
F38R0JR742
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LUMEFANTRINE
DASH   HSDB   INN   MART.   MI   ORANGE BOOK   USAN   USP-RS   VANDF   WHO-DD   WHO-IP  
USAN   INN  
Official Name English
LUMEFANTRINE COMPONENT OF COARTEM
Brand Name English
COARTEM COMPONENT LUMEFANTRINE
Brand Name English
LUMEFANTRINE [VANDF]
Common Name English
DL-BENFLUMELOL
Common Name English
LUMEFANTRINE [HSDB]
Common Name English
BENFLUMELOL
Common Name English
LUMEFANTRINUM [WHO-IP LATIN]
Common Name English
LUMEFANTRINE [INN]
Common Name English
GNF-PF-1971
Code English
LUMEFANTRINE [MART.]
Common Name English
9H-FLUORENE-4-METHANOL, 2,7-DICHLORO-9-((4-CHLOROPHENYL)METHYLENE)-.ALPHA.-((DIBUTYLAMINO)METHYL)-, (Z)-
Systematic Name English
LUMEFANTRINE [JAN]
Common Name English
LUMEFANTRINE [USP MONOGRAPH]
Common Name English
BENFLUMETOL
Common Name English
LUMEFANTRINE [MI]
Common Name English
LUMEFANTRINE [USAN]
Common Name English
LUMEFANTRINE [WHO-DD]
Common Name English
(+/-)-2,7-DICHLORO-9-((Z)-P-CHLOROBENZYLIDENE)-.ALPHA.((DIBUTYLAMINO)METHYL)FLUORENE-4-METHANOL
Common Name English
CPG-56695
Code English
LUMEFANTRINE [USP-RS]
Common Name English
2-DIBUTYLAMINO-1-(2,7-DICHLORO-9-(1-(4-CHLOROPHENYL)METH-(Z)-YLIDENE)-9H-FLUOREN-4-YL)ETHANOL
Common Name English
LUMEFANTRINE [ORANGE BOOK]
Common Name English
LUMEFANTRINE [WHO-IP]
Common Name English
Classification Tree Code System Code
LIVERTOX 577
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 6.5.3.1 (ART/LUM)
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
NDF-RT N0000175482
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
WHO-ATC P01BF01
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
FDA ORPHAN DRUG 245507
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
EU-Orphan Drug EU/3/09/702
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
Code System Code Type Description
USP_CATALOG
1370746
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
PRIMARY USP-RS
DRUG CENTRAL
1617
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
PRIMARY
MERCK INDEX
M6927
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
PRIMARY Merck Index
HSDB
7210
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
PRIMARY
NCI_THESAURUS
C81541
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
PRIMARY
EVMPD
SUB08618MIG
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
PRIMARY
FDA UNII
F38R0JR742
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
PRIMARY
INN
7610
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
PRIMARY
PUBCHEM
6437380
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
PRIMARY
RXCUI
847728
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
PRIMARY RxNorm
EPA CompTox
82186-77-4
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
PRIMARY
CAS
204133-10-8
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
NON-SPECIFIC STEREOCHEMISTRY
ChEMBL
CHEMBL422330
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
PRIMARY
MESH
C102070
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
PRIMARY
CAS
120583-69-9
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
SUPERSEDED
LACTMED
Artemether and Lumefantrine
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
PRIMARY
DRUG BANK
DB06708
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
PRIMARY
CAS
82186-77-4
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
LUMEFANTRINE
Created by admin on Sat Jun 26 13:49:04 UTC 2021 , Edited by admin on Sat Jun 26 13:49:04 UTC 2021
PRIMARY Description: A yellow crystalline powder.Solubility: Practically insoluble in water; soluble in dichloromethane R; slightly soluble in methanol R .Category: Antimalarial.Storage: Lumefantrine should be kept in a well-closed container.Additional information. Lumefantrine melts at 128?132?C.Definition: Lumefantrine contains not less than 98.5% and not more than 101.0% of C30H32Cl3NO, calculated with reference to the dried substance.
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
MAJOR
ENANTIOMER -> RACEMATE
METABOLIC ENZYME -> INHIBITOR
In vitro, lumefantrine significantly inhibits the activity of CYP2D6 at therapeutic plasma concentrations
ENANTIOMER -> RACEMATE
BINDER->LIGAND
BINDING
Related Record Type Details
METABOLITE -> PARENT
In human liver microsomes and in recombinant CYP450 enzymes, lumefantrine was metabolized mainly by CYP3A4 to desbutyl-lumefantrine
PLASMA
Related Record Type Details
IMPURITY -> PARENT
IMPURITY -> PARENT
IMPURITY -> PARENT
LUMEFANTRINE Impurity A. The impurity peaks are eluted at the following relative retention with reference to lumefantrine (retention time about 10 minutes): impurity A about 0.9.
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC in patients with P. falciparum malaria

Biological Half-life PHARMACOKINETIC in healthy volunteers

Tmax PHARMACOKINETIC