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
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
Molecular Formula | C15H22O5 |
Molecular Weight | 282.3322 |
Charge | 0 |
Count |
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Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 7 / 7 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: http://apps.who.int/medicinedocs/en/d/Jh2922e/2.5.12.html#Jh2922e.2.5.12http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001199/WC500118113.pdfhttp://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022268s012lbl.pdfCurator'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
Sources: http://apps.who.int/medicinedocs/en/d/Jh2922e/2.5.12.html#Jh2922e.2.5.12http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001199/WC500118113.pdfhttp://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022268s012lbl.pdf
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
Sources: https://www.springboard4health.com/notebook/nutrients_artemisinin.html https://www.drlam.com/blog/artemisinin-cancer-research/19627/https://www.ncbi.nlm.nih.gov/pubmed/12499215http://www.ncbi.nlm.nih.gov/pubmed/12499215
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
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL364 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25148516 |
5.5 nM [EC50] | ||
Target ID: CHEMBL612653 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11141088 |
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Target ID: CHEMBL364 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18823976 |
24.0 nM [IC50] | ||
Target ID: PfATP6, Plasmodium falciparum Sources: https://www.ncbi.nlm.nih.gov/pubmed/17145800 |
79.0 nM [IC50] | ||
Target ID: CHEMBL612888 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27380994 |
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Target ID: CHEMBL613897 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Eurartesim Approved UseEurartesim 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. |
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Curative | Eurartesim Approved UseEurartesim 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. |
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Curative | Artemisinin Approved UseTreatment 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 Date4.7329919E11 |
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Curative | COARTEM Approved UseCoartem (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 Date1.23906241E12 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse 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
AE | Significance | Dose | Population |
---|---|---|---|
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
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 14.0 |
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 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022268s000_ClinPharmR.pdf#page=21 Page: 21.0 |
minor | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022268s000_ClinPharmR.pdf#page=21 Page: 21.0 |
minor | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022268s000_ClinPharmR.pdf#page=21 Page: 21.0 |
minor |
PubMed
Title | Date | PubMed |
---|---|---|
Demonstrating the validity of natural products as anti-infective drugs. | 2001 |
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In vivo-in vitro model for the assessment of clinically relevant antimalarial cross-resistance. | 2001 Dec |
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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 |
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Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. | 2001 Jan |
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A comparison of the in vivo kinetics of Plasmodium falciparum ring-infected erythrocyte surface antigen-positive and -negative erythrocytes. | 2001 Jul 15 |
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Rational use of drugs against Plasmodium falciparum. | 2001 Jul-Aug |
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Radical mechanism of action of the artemisinin-type compounds. | 2001 Jun |
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Malaria epidemic in Burundi. | 2001 Mar 31 |
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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 |
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Chlorproguanil-dapsone (LAPDAP) for uncomplicated falciparum malaria. | 2001 Nov |
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Artesunate and praziquantel for the treatment of Schistosoma haematobium infections: a double-blind, randomized, placebo-controlled study. | 2001 Nov 15 |
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Fluoro artemisinins: difluoromethylene ketones. | 2001 Nov 16 |
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Multiple dose study of interactions between artesunate and artemisinin in healthy volunteers. | 2001 Oct |
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Assessment of susceptibility of Plasmodium falciparum to chloroquine, quinine, mefloquine, sulfadoxine-pyrimethamine and artemisinin in southern Viet Nam. | 2001 Sep-Oct |
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[Study on treatment of multi-drug resistant falciparum malaria by using a combination of dihydroartemisinin and pyronaridine]. | 2002 |
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[Therapeutic effect of dihydroartemisinin combined with naphthoquine phosphate in patients with falciparum malaria]. | 2002 |
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Relative bioavailability of artesunate and dihydroartemisinin: investigations in the isolated perfused rat liver and in healthy Caucasian volunteers. | 2002 Feb |
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Mechanism-based design of parasite-targeted artemisinin derivatives: synthesis and antimalarial activity of new diamine containing analogues. | 2002 Feb 28 |
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Management of malaria in Thailand. | 2002 Mar |
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Heme-artemisinin adducts are crucial mediators of the ability of artemisinin to inhibit heme polymerization. | 2002 Mar |
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Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement? | 2002 Mar 25 |
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How might qinghaosu (artemisinin) and related compounds kill the intraerythrocytic malaria parasite? A chemist's view. | 2002 May |
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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 |
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Synthesis and cytotoxicity of dihydroartemisinin ethers containing cyanoarylmethyl group. | 2003 Mar 20 |
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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 |
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Activity of dihydroartemisinin against Leishmania donovani both in vitro and vivo. | 2004 Aug |
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Clinical pharmacokinetics of the diastereomers of arteether in healthy volunteers. | 2005 |
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Dihydroartemisinin is cytotoxic to papillomavirus-expressing epithelial cells in vitro and in vivo. | 2005 Dec 1 |
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Development and validation of a high-performance liquid chromatography-mass spectroscopy assay for determination of artesunate and dihydroartemisinin in human plasma. | 2005 Feb 25 |
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Pharmacokinetics of the four combination regimens of dihydroartemisinin/mefloquine in acute uncomplicated falciparum malaria. | 2005 Jan |
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Antimalarial drugs: QT prolongation and cardiac arrhythmias. | 2005 May |
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The therapeutic potential of semi-synthetic artemisinin and synthetic endoperoxide antimalarial agents. | 2005 Sep |
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Manslaughter by fake artesunate in Asia--will Africa be next? | 2006 Jun |
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In-vitro susceptibility of Plasmodium falciparum to monodesethylamodiaquine, dihydroartemisinin and quinine in an area of high chloroquine resistance in Rwanda. | 2006 Jun |
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Re-evaluation of how artemisinins work in light of emerging evidence of in vitro resistance. | 2006 May |
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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 |
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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 |
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1440803
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
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on
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Record UNII |
9RMU91N5K2
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Record Status |
Validated (UNII)
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DSLD |
2508 (Number of products:21)
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LIVERTOX |
64
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WHO-ATC |
P01BE01
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NCI_THESAURUS |
C277
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369397
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9RMU91N5K2
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ARTEMISININ
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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. | ||
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DTXSID2040652
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3871
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2367409
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DB13132
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C78093
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C031327
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5954
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ARTEMISININ
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63968-64-9
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m2077
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9RMU91N5K2
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68827
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100000086624
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223316
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SUB05575MIG
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CHEMBL567597
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1042747
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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)
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ACTIVE MOIETY |
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