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

Details

Stereochemistry ABSOLUTE
Molecular Formula C16H26O5
Molecular Weight 298.3746
Optical Activity UNSPECIFIED
Defined Stereocenters 8 / 8
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ARTEMETHER

SMILES

[H][C@@]12CC[C@@H](C)[C@]3([H])CC[C@]4(C)OO[C@@]13[C@]([H])(O[C@H](OC)[C@@H]2C)O4

InChI

InChIKey=SXYIRMFQILZOAM-HVNFFKDJSA-N
InChI=1S/C16H26O5/c1-9-5-6-12-10(2)13(17-4)18-14-16(12)11(9)7-8-15(3,19-14)20-21-16/h9-14H,5-8H2,1-4H3/t9-,10-,11+,12+,13+,14-,15-,16-/m1/s1

HIDE SMILES / InChI

Molecular Formula C16H26O5
Molecular Weight 298.3746
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 8 / 8
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including: http://www.drugbank.ca/drugs/DB06697 http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7866ec19-dfac-47d4-a53f-511a12643cbf

Artemether is an antimalarial agent used to treat acute uncomplicated malaria. It is administered in combination with lumefantrine for improved efficacy against malaria. Artemether is rapidly metabolized into an active metabolite dihydroartemisinin (DHA). The antimalarial activity of artemether and DHA has been attributed to endoperoxide moiety. Artemethe involves an interaction with ferriprotoporphyrin IX (“heme”), or ferrous ions, in the acidic parasite food vacuole, which results in the generation of cytotoxic radical species. The generally accepted mechanism of action of peroxide antimalarials involves interaction of the peroxide-containing drug with heme, a hemoglobin degradation byproduct, derived from proteolysis of hemoglobin. This interaction is believed to result in the formation of a range of potentially toxic oxygen and carbon-centered radicals. Other mechanisms of action for artemether include their ability to reduce fever by production of signals to hypothalamus thermoregulatory center. Now, recent research has shown the presence of a new, previously unknown cyclooxygenase enzyme COX-3, found in the brain and spinal cord, which is selectively inhibited by artemether, and is distinct from the two already known cyclooxygenase enzymes COX-1 and COX-2. It is now believed that this selective inhibition of the enzyme COX-3 in the brain and spinal cord explains the ability of artemether in relieving pain and reducing fever which is produced by malaria. The most common adverse reactions in adults (>30%) are headache, anorexia, dizziness, asthenia, arthralgia and myalgia.

CNS Activity

Curator's Comment: Meningeal inflammation increases artemether concentrations in cerebrospinal fluid in сhildrens treated with intramuscular artemether. http://aac.asm.org/content/55/11/5027.full

Originator

Sources: https://www.ncbi.nlm.nih.gov/pubmed/21989013Kexue Tongbao (Chinese Edition) (1979), 24, (14), 667-9.
Curator's Comment: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778258/

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Eurartesim

Approved Use

Eurartesim is indicated for the treatment of uncomplicated Plasmodium falciparum malaria in adults, adolescents, children and infants 6 months and over and weighing 5 kg or more.
Curative
Eurartesim

Approved Use

Eurartesim is indicated for the treatment of uncomplicated Plasmodium falciparum malaria in adults, adolescents, children and infants 6 months and over and weighing 5 kg or more.
Curative
Artemisinin

Approved Use

Treatment of uncomplicated falciparum malaria in areas where there is evidence that chloroquine, pyrimethamine/sulfadoxine, mefloquine and quinine are ineffective. It should always be administered together with mefloquine in full therapeutic dose.

Launch Date

1984
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

2009
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
60 ng/mL
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ARTEMETHER plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
146 ng × h/mL
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ARTEMETHER plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.6 h
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ARTEMETHER plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
4.6%
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ARTEMETHER plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
80 mg 3 times / day multiple, oral
Recommended
Dose: 80 mg, 3 times / day
Route: oral
Route: multiple
Dose: 80 mg, 3 times / day
Co-administed with::
lumefantrine, p.o(480 mg, b.i.d)
Sources: Page: p.3
unhealthy
Health Status: unhealthy
Condition: Plasmodium falciparum malaria
Sources: Page: p.3
Disc. AE: QT interval prolonged...
AEs leading to
discontinuation/dose reduction:
QT interval prolonged
Sources: Page: p.3
80 mg 3 times / day multiple, oral
Recommended
Dose: 80 mg, 3 times / day
Route: oral
Route: multiple
Dose: 80 mg, 3 times / day
Co-administed with::
lumefantrine, p.o(480 mg, b.i.d)
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Plasmodium falciparum malaria
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
QT interval prolonged Disc. AE
80 mg 3 times / day multiple, oral
Recommended
Dose: 80 mg, 3 times / day
Route: oral
Route: multiple
Dose: 80 mg, 3 times / day
Co-administed with::
lumefantrine, p.o(480 mg, b.i.d)
Sources: Page: p.3
unhealthy
Health Status: unhealthy
Condition: Plasmodium falciparum malaria
Sources: Page: p.3
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: administration of ketoconazole le to an increase in artemether (2.3-fold), dihydroartemisinin (1.5 fold), and lumefantrine (1.6-fold) exposure in healthy subjects;
Page: 14.0
minor
minor
minor
PubMed

PubMed

TitleDatePubMed
Gas concentration effects on secondary metabolite production by plant cell cultures.
2001
Pharmacokinetic interactions of antimalarial agents.
2001
The anti-malarial artesunate is also active against cancer.
2001 Apr
Severe falciparum malaria in five soldiers from East Timor: a case series and literature review.
2001 Aug
New trends in extraction, identification and quantification of artemisinin and its derivatives.
2001 Dec
Why artemisinin and certain synthetic peroxides are potent antimalarials. Implications for the mode of action.
2001 Dec
Authentication of artemether, artesunate and dihydroartemisinin antimalarial tablets using a simple colorimetric method.
2001 Dec
A comparison of oral artesunate and artemether antimalarial bioactivities in acute falciparum malaria.
2001 Dec
Mode of action and mechanisms of resistance for antimalarial drugs.
2001 Feb
Amorpha-4,11-diene synthase: cloning and functional expression of a key enzyme in the biosynthetic pathway of the novel antimalarial drug artemisinin.
2001 Feb
[Acute schistosomiasis: fever and eosinophilia, with or without urticaria, after a trip to Africa].
2001 Feb 3
In vitro evidence for auto-induction of artemisinin metabolism in the rat.
2001 Jul-Sep
Malaria epidemic in Burundi.
2001 Mar 31
New manzamine alkaloids with potent activity against infectious diseases.
2001 Mar 7
In vitro susceptibility of Plasmodium falciparum isolates from Myanmar to antimalarial drugs.
2001 Nov
Chlorproguanil-dapsone (LAPDAP) for uncomplicated falciparum malaria.
2001 Nov
'To search and studdy out the secrett of tropical diseases by way of experiment'.
2001 Nov-Dec
In vitro beta-hematin formation assays with plasma of mice infected with Plasmodium yoelii and other parasite preparations: comparative inhibition with quinoline and endoperoxide antimalarials.
2001 Oct 26
Improved oral bioavailability of artemisinin through inclusion complexation with beta- and gamma-cyclodextrins.
2001 Oct 4
Synthesis of new artemisinin analogues from artemisinic acid modified at C-3 and C-13 and their antimalarial activity.
2001 Sep
Chemotherapeutic approaches to protozoa: haemosporina--current level of knowledge and outlook.
2001 Sep
Fourier transform infrared investigation of non-heme Fe(III) and Fe(II) decomposition of artemisinin and of a simplified trioxane alcohol.
2001 Sep 13
Combination therapy for malaria: the way forward?
2002
[Study on treatment of multi-drug resistant falciparum malaria by using a combination of dihydroartemisinin and pyronaridine].
2002
[Therapeutic effect of dihydroartemisinin combined with naphthoquine phosphate in patients with falciparum malaria].
2002
Epidemiology of drug-resistant malaria.
2002 Apr
Clinical status and implications of antimalarial drug resistance.
2002 Feb
Anhydrodihydroartemisinin and its 10-trifluoromethyl analogue: access to novel d-ring-contracted artemisinin trifluoromethyl ketones.
2002 Feb 22
In vitro antiprotozoal effects of artemisinin on Neospora caninum.
2002 Jan 3
Development and validation of a high-performance liquid chromatography-mass spectrometry assay for the determination of artemether and its metabolite dihydroartemisinin in human plasma.
2002 Jul 15
Heme-artemisinin adducts are crucial mediators of the ability of artemisinin to inhibit heme polymerization.
2002 Mar
Activity of drugs from traditional Chinese medicine toward sensitive and MDR1- or MRP1-overexpressing multidrug-resistant human CCRF-CEM leukemia cells.
2002 Mar-Apr
The effect of 10 alpha-trifluoromethylhydroartemisinin on Plasmodium berghei infection and its toxicity in experimental animals.
2002 Nov-Dec
A comparative clinical trial of combinations of dihydroartemisinin plus azithromycin and dihydroartemisinin plus mefloquine for treatment of multidrug resistant falciparum malaria.
2002 Sep
Effect of dihydroartemisinin on the antioxidant capacity of P. falciparum-infected erythrocytes.
2003 Dec
Synthesis and cytotoxicity of dihydroartemisinin ethers containing cyanoarylmethyl group.
2003 Mar 20
CV8, a new combination of dihydroartemisinin, piperaquine, trimethoprim and primaquine, compared with atovaquone-proguanil against falciparum malaria in Vietnam.
2004 Feb
Pharmacokinetics of artesunate following oral and rectal administration in healthy Sudanese volunteers.
2004 Jul
Experimental designed optimisation and stability evaluation of dry suspensions with artemisinin derivatives for paediatric use.
2004 Sep 28
Drug sensitivity of Plasmodium falciparum along the Thai-Myanmar border using the new field-deployable HRP2 in vitro assay.
2005
Clinical pharmacokinetics of the diastereomers of arteether in healthy volunteers.
2005
Development and validation of a high-performance liquid chromatography-mass spectroscopy assay for determination of artesunate and dihydroartemisinin in human plasma.
2005 Feb 25
Investigation of bioavailability, pharmacokinetics and safety of new pediatric formulations of artesunate and mefloquine.
2005 Jan
Synergistic cytotoxicity of artemisinin and sodium butyrate on human cancer cells.
2005 Nov-Dec
[Effect of dihydroartemisinin on ultrastructure of Giardia lamblia in vitro].
2005 Oct 30
Association of failures of seven-day courses of artesunate in a non-immune population in Bangui, Central African Republic with decreased sensitivity of Plasmodium falciparum.
2005 Sep
The therapeutic potential of semi-synthetic artemisinin and synthetic endoperoxide antimalarial agents.
2005 Sep
Pharmacokinetics of the diastereomers of arteether, a potent antimalarial drug, in rats.
2005 Sep
Dihydroartemisinin enhances radiosensitivity of human glioma cells in vitro.
2006 Feb
Effects of the antimalarial drug dihydroartemisinin (DHA) on rat embryos in vitro.
2006 Jan
Patents

Sample Use Guides

Adults and children: 25 mg/kg on the first day followed by 12.5 mg/kg on the second and third days in combination with mefloquine (15 mg/kg) in a single dose on the second day. In some areas, a higher dose (25 mg/kg) of mefloquine may be required for a cure to be obtained.
Route of Administration: Oral
In Vitro Use Guide
Artemisinine was active against 3 chloroquine-resistant strains of Plasmodium falciparum, strains K1 and T996 from Thailand and LS21 from India, with complete growth inhibition at 10(-7) M.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:40:12 GMT 2023
Edited
by admin
on Fri Dec 15 15:40:12 GMT 2023
Record UNII
C7D6T3H22J
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ARTEMETHER
DASH   HSDB   INN   MART.   MI   ORANGE BOOK   USAN   USP-RC   USP-RS   VANDF   WHO-DD   WHO-IP  
USAN   INN  
Official Name English
.BETA.-ARTEMETHER
Common Name English
NSC-665970
Code English
GVITHER
Common Name English
(+)-ARTEMETHER
Common Name English
ARTEMETHER [JAN]
Common Name English
COARTEM COMPONENT ARTEMETHER
Brand Name English
SM224
Code English
ARTEMETHER [MART.]
Common Name English
(3R,5aS,6R,8aS,9R,10S,12R,12aR)-10-Methoxy-3,6,9-trimethyldecahydro-3,12-epoxypyrano[4,3-j]-1,2-benzodioxepine
Common Name English
ARTEMETHERUM [WHO-IP LATIN]
Common Name English
MALARTEM
Common Name English
NSC-759820
Code English
(3R,5AS,6R,8AS,9R,10S,12R,12AR)-DECAHYDRO-10-METHOXY-3,6,9-TRIMETHYL-3,12-EPOXY-12H-PYRANO(4,3-J)-1,2-BENZODIOXEPIN
Systematic Name English
ARTEMETHER [HSDB]
Common Name English
ARTESAPH
Common Name English
LARITHER
Common Name English
ARTEMETHER [USAN]
Common Name English
FALCIDOL
Common Name English
PALUTHER
Common Name English
3,12-EPOXY-12H-PYRANO(4,3-J)-1,2-BENZODIOXEPIN, DECAHYDRO-10-METHOXY-3,6,9-TRIMETHYL-, (3R,5AS,6R,8AS,9R,10S,12R,12AR)-
Common Name English
ARTEMETHER [USP-RS]
Common Name English
Artemether [WHO-DD]
Common Name English
artemether [INN]
Common Name English
.BETA.-DIHYDROARTEMISININ METHYL ETHER
Common Name English
ARTEMETHER [MI]
Common Name English
ARTEMETHER [VANDF]
Common Name English
ARTEMETHER [WHO-IP]
Common Name English
ARTEMETHER COMPONENT OF COARTEM
Brand Name English
ARTEMETHER [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
WHO-ATC P01BF01
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
WHO-ESSENTIAL MEDICINES LIST 6.5.3.1
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
NDF-RT N0000175482
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
FDA ORPHAN DRUG 245507
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
WHO-ATC P01BE02
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
WHO-ESSENTIAL MEDICINES LIST 6.5.3.1 (ART/LUM)
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
EU-Orphan Drug EU/3/09/702
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
NCI_THESAURUS C271
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
Code System Code Type Description
FDA UNII
C7D6T3H22J
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY
WIKIPEDIA
ARTEMETHER
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY
PUBCHEM
68911
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY
ChEMBL
CHEMBL566534
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY
MESH
C032942
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY
NSC
665970
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY
RXCUI
18343
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY RxNorm
LACTMED
Artemether and Lumefantrine
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY
EVMPD
SUB05574MIG
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY
CHEBI
195280
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY
DAILYMED
C7D6T3H22J
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY
RS_ITEM_NUM
1042780
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY
MERCK INDEX
m2075
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY Merck Index
NCI_THESAURUS
C73001
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY
EPA CompTox
DTXSID7040651
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY
DRUG BANK
DB06697
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY
HSDB
7456
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
ARTEMETHER
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY Description: White crystals or a white, crystalline powder. Solubility: Practically insoluble in water; very soluble in dichloromethane R and acetone R; freely soluble in ethyl acetate R and dehydrated ethanol R. Category: Antimalarial drug. Storage: Artemether should be kept in a tightly closed container and protected from light. Labelling: The designation Artemether for parenteral use indicates that the substance complies with the additional requirements and may be used for parenteral administration. Additional information: The parenteral form is normally intended for intramuscular administration. Requirement: Artemether contains not less than 97.0% and not more than the equivalent of 102.0% of C16H26O5 using ?Assay?, method A, andnot less than 98.0% and not more than the equivalent of 102.0% of C16H26O5 using ?Assay?, method B, both calculated with reference to the dried substance.
NSC
759820
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY
USAN
UU-173
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY
INN
6458
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY
SMS_ID
100000092762
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY
DRUG CENTRAL
245
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY
CAS
71963-77-4
Created by admin on Fri Dec 15 15:40:12 GMT 2023 , Edited by admin on Fri Dec 15 15:40:12 GMT 2023
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
MAJOR
METABOLIC ENZYME -> SUBSTRATE
MINOR
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
MINOR
METABOLIC ENZYME -> SUBSTRATE
MINOR
Related Record Type Details
METABOLITE -> PARENT
METABOLITE ACTIVE -> PRODRUG
METABOLITE -> PARENT
METABOLITE -> PARENT
Related Record Type Details
IMPURITY -> PARENT
IMPURITY -> PARENT
IMPURITY -> PARENT
IMPURITY -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC