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

Details

Stereochemistry ABSOLUTE
Molecular Formula C15H22O5
Molecular Weight 282.3322
Optical Activity UNSPECIFIED
Defined Stereocenters 7 / 7
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ARTEMISININ

SMILES

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

InChI

InChIKey=BLUAFEHZUWYNDE-NNWCWBAJSA-N
InChI=1S/C15H22O5/c1-8-4-5-11-9(2)12(16)17-13-15(11)10(8)6-7-14(3,18-13)19-20-15/h8-11,13H,4-7H2,1-3H3/t8-,9-,10+,11+,13-,14-,15-/m1/s1

HIDE SMILES / InChI

Molecular Formula C15H22O5
Molecular Weight 282.3322
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 7 / 7
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

4.7329919E11
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
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
Demonstrating the validity of natural products as anti-infective drugs.
2001
In vivo-in vitro model for the assessment of clinically relevant antimalarial cross-resistance.
2001 Dec
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
Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s.
2001 Jan
A comparison of the in vivo kinetics of Plasmodium falciparum ring-infected erythrocyte surface antigen-positive and -negative erythrocytes.
2001 Jul 15
Rational use of drugs against Plasmodium falciparum.
2001 Jul-Aug
Radical mechanism of action of the artemisinin-type compounds.
2001 Jun
Malaria epidemic in Burundi.
2001 Mar 31
Resistance of Plasmodium falciparum to antimalarial drugs in a highly endemic area of southern Viet Nam: a study in vivo and in vitro.
2001 May-Jun
Chlorproguanil-dapsone (LAPDAP) for uncomplicated falciparum malaria.
2001 Nov
Artesunate and praziquantel for the treatment of Schistosoma haematobium infections: a double-blind, randomized, placebo-controlled study.
2001 Nov 15
Fluoro artemisinins: difluoromethylene ketones.
2001 Nov 16
Multiple dose study of interactions between artesunate and artemisinin in healthy volunteers.
2001 Oct
Assessment of susceptibility of Plasmodium falciparum to chloroquine, quinine, mefloquine, sulfadoxine-pyrimethamine and artemisinin in southern Viet Nam.
2001 Sep-Oct
[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
Relative bioavailability of artesunate and dihydroartemisinin: investigations in the isolated perfused rat liver and in healthy Caucasian volunteers.
2002 Feb
Mechanism-based design of parasite-targeted artemisinin derivatives: synthesis and antimalarial activity of new diamine containing analogues.
2002 Feb 28
Management of malaria in Thailand.
2002 Mar
Heme-artemisinin adducts are crucial mediators of the ability of artemisinin to inhibit heme polymerization.
2002 Mar
Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?
2002 Mar 25
How might qinghaosu (artemisinin) and related compounds kill the intraerythrocytic malaria parasite? A chemist's view.
2002 May
Comparative clinical trial of two-fixed combinations dihydroartemisinin-napthoquine-trimethoprim (DNP) and artemether-lumefantrine (Coartem/Riamet) in the treatment of acute uncomplicated falciparum malaria in Thailand.
2003 Jun
Synthesis and cytotoxicity of dihydroartemisinin ethers containing cyanoarylmethyl group.
2003 Mar 20
An HPLC-MS method for simultaneous estimation of alpha,beta-arteether and its metabolite dihydroartemisinin, in rat plasma for application to pharmacokinetic study.
2003 Oct
Activity of dihydroartemisinin against Leishmania donovani both in vitro and vivo.
2004 Aug
Clinical pharmacokinetics of the diastereomers of arteether in healthy volunteers.
2005
Dihydroartemisinin is cytotoxic to papillomavirus-expressing epithelial cells in vitro and in vivo.
2005 Dec 1
Development and validation of a high-performance liquid chromatography-mass spectroscopy assay for determination of artesunate and dihydroartemisinin in human plasma.
2005 Feb 25
Pharmacokinetics of the four combination regimens of dihydroartemisinin/mefloquine in acute uncomplicated falciparum malaria.
2005 Jan
Antimalarial drugs: QT prolongation and cardiac arrhythmias.
2005 May
The therapeutic potential of semi-synthetic artemisinin and synthetic endoperoxide antimalarial agents.
2005 Sep
Manslaughter by fake artesunate in Asia--will Africa be next?
2006 Jun
In-vitro susceptibility of Plasmodium falciparum to monodesethylamodiaquine, dihydroartemisinin and quinine in an area of high chloroquine resistance in Rwanda.
2006 Jun
Re-evaluation of how artemisinins work in light of emerging evidence of in vitro resistance.
2006 May
Pharmacokinetics of piperaquine after repeated oral administration of the antimalarial combination CV8 in 12 healthy male subjects.
2006 May
Two-step synthesis of achiral dispiro-1,2,4,5-tetraoxanes with outstanding antimalarial activity, low toxicity, and high-stability profiles.
2008 Apr 10
Fetal bovine serum and human constitutive androstane receptor: evidence for activation of the SV23 splice variant by artemisinin, artemether, and arteether in a serum-free cell culture system.
2014 Jun 1
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 16:05:50 UTC 2023
Edited
by admin
on Fri Dec 15 16:05:50 UTC 2023
Record UNII
9RMU91N5K2
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ARTEMISININ
INCI   INN   MART.   MI   USP-RS   WHO-DD   WHO-IP  
INN   INCI  
Official Name English
QING HAU SAU
Common Name English
GNF-PF-5341
Code English
ARTEMISININUM [WHO-IP LATIN]
Common Name English
ARTEMISININ [MART.]
Common Name English
HUANGHUAHAOSU
Common Name English
artemisinin [INN]
Common Name English
ARTEMISININ [INCI]
Common Name English
Artemisinin [WHO-DD]
Common Name English
ARTEMISININ [WHO-IP]
Common Name English
NSC-369397
Code English
ARTEMISININ [MI]
Common Name English
ARTEMISININ [USP-RS]
Common Name English
(3R,5AS,6R,8AS,9R,12S,12AR)-3,6,9-TRIMETHYLOCTAHYDRO-3,12-EPOXYPYRANO(4,3-J )-1,2-BENZODIOXEPIN-10(3H)-ONE
Systematic Name English
(3R,5AS,6R,8AS,9R,12S,12AR)-OCTAHYDRO-3,6,9-TRIMETHYL-3,12-EPOXY-12H-PYRANO(4,3-J)-1,2-BENZODIOXEPIN-10(3H)-ONE
Common Name English
Classification Tree Code System Code
DSLD 2508 (Number of products:21)
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
LIVERTOX 64
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
WHO-ATC P01BE01
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
NCI_THESAURUS C277
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
Code System Code Type Description
NSC
369397
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
PRIMARY
DAILYMED
9RMU91N5K2
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
ARTEMISININ
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
PRIMARY Description: Colourless needles or white crystalline powder. Solubility: Practically insoluble in water; very soluble in dichloromethane R; freely soluble in acetone R and ethyl acetate R; soluble in glacial acetic acid R, methanol R and ethanol (~750 g/L) TS. Category: Antimalarial. Storage: Artemisinin should be kept in a well-closed container and protected from light. Requirement: Artemisinin contains not less than 97.0% and not more than 102.0% of C15H22O5, calculated with reference to the dried substance.
EPA CompTox
DTXSID2040652
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
PRIMARY
DRUG CENTRAL
3871
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
PRIMARY
RXCUI
2367409
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PRIMARY
DRUG BANK
DB13132
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
PRIMARY
NCI_THESAURUS
C78093
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
PRIMARY
MESH
C031327
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
PRIMARY
INN
5954
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
PRIMARY
WIKIPEDIA
ARTEMISININ
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
PRIMARY
CAS
63968-64-9
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
PRIMARY
MERCK INDEX
m2077
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
PRIMARY Merck Index
FDA UNII
9RMU91N5K2
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
PRIMARY
PUBCHEM
68827
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
PRIMARY
SMS_ID
100000086624
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
PRIMARY
CHEBI
223316
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
PRIMARY
EVMPD
SUB05575MIG
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
PRIMARY
ChEMBL
CHEMBL567597
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
PRIMARY
RS_ITEM_NUM
1042747
Created by admin on Fri Dec 15 16:05:50 UTC 2023 , Edited by admin on Fri Dec 15 16:05:50 UTC 2023
PRIMARY
Related Record Type Details
DERIVATIVE -> PARENT
Related Record Type Details
METABOLITE ACTIVE -> PRODRUG
Related Record Type Details
PARENT -> IMPURITY
PARENT -> IMPURITY
In the chromatogram obtained with solution (1): the area of any peak corresponding to impurity B (artemisinin) is not greater than 0.5 times the area of the principal peak obtained with solution (4) (0.5%).
CHROMATOGRAPHIC PURITY (HPLC/UV)
IMPURITY -> PARENT
IMPURITY -> PARENT
Related Record Type Details
ACTIVE MOIETY