Artemether: Difference between revisions

| Verifiedfields = changed

| verifiedrevid = 399532235

| IUPAC_name =

| image = artemether.svg

| tradename =

| Drugs.com = {{drugs.com|international|artemether}}

| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->

| pregnancy_US = C

| pregnancy_category =

| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->

| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->

| legal_UK = POM

| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->

| legal_status =

| routes_of_administration = Oral

| bioavailability =

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| metabolism =

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| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = <!-- blanked - oldvalue: 71963-77-4 -->

| ATC_prefix = P01

| ATC_suffix = BE02

| ATC_supplemental =

| PubChem = 68911

| DrugBank_Ref = {{drugbankcite|changed|drugbank}}

| DrugBank = DB06697

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 62138

| UNII_Ref = {{fdacite|changed|FDA}}

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| KEGG_Ref = {{keggcite|changed|kegg}}

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| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 195280

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = <!-- blanked - oldvalue: 1237051 -->

| chemical_formula =

| C=16 | H=26 | O=5

| molecular_weight = 298.374 g/mol

| smiles = C[C@@H]1CC[C@@H]3C42OO[C@](C)(CC[C@@H]12)O[C@H]4O[C@H](OC)[C@@H]3C

| InChI = 1/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

| InChIKey = SXYIRMFQILZOAM-LJXHFVHTBB

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 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

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = SXYIRMFQILZOAM-HVNFFKDJSA-N

'''Artemether''' ([[International Nonproprietary Name|INN]]) is an antimalarial for the treatment of multi-drug resistant strains of ''[[Plasmodium falciparum|falciparum]]'' [[malaria]]. It is combined with [[Lumefantrine]] and sold by [[Novartis]] under the brand names Riamet and Co-Artem.

==Chemical nature==

It is a [[methyl ether]] derivative of [[artemisinin]], which is a peroxide [[lactone]] isolated from the [[China|Chinese]] antimalarial plant, ''[[Artemisia annua]]''. It is also known as dihydroartemisinin methyl ether, but its [[International Union of Pure and Applied Chemistry|correct chemical nomenclature]] is (+)-(3-alpha,5a-beta,6-beta,8a-beta, 9-alpha,12-beta,12aR)-decahydro-10-methoxy-3,6,9-trimethyl-3,12-epoxy-12H-pyrano(4,3-j)-1,2-benzodioxepin.

==Uses==

===Antimalarial===

Artemether is highly effective against the blood [[schizont]]s of both [[plasmodium|malarial parasites]] ''[[plasmodium falciparum|P. falciparum]]'' and ''[[plasmodium vivax|P. vivax]]''. It is applied in combination with [[lumefantrine]] in clinical treatments of [[malaria]]. [[World Health Organization]] guidelines for the treatment of uncomplicated [[plasmodium falciparum|falciparum malaria]] recommend the use of this [[artemisinin]]-based combination therapy, and approved by [[Swissmedic]] in December 2008 and recently approved by the [[United States]] [[Food and Drug Administration]]. [[Zambia]] was the first African country to adopt artemether/[[lumefantrine]] (commonly called Coartem) as first-line therapy in national malaria treatment guidelines in 2002. Clinical records show that by 2008, the rates of in-patient [[malaria]] cases and deaths decreased by 61% and 66%, respectively, compared with the 2001-2002 reference period. In [[South Africa]] also the number of [[malaria]]-related outpatient cases and hospital admissions to each fall by 99% from 2001 to 2003, and [[malaria]]-related deaths decreased by 97% over the same period.<ref>{{cite journal |doi=10.1186/1475-2875-8-S1-S8 |author=Barnes KI, Chanda P, Ab Barnabas G |year=2009 |title=Impact of the large-scale deployment of artemether/lumefantrine on the malaria disease burden in Africa: case studies of South Africa, Zambia and Ethiopia |journal=Malar J. |volume=8 |issue=1 |pages=S8 |pmid=119818175 |url=http://www.malariajournal.com/content/8%20Suppl%201//S8}}</ref> The efficacy of the six-dose regimen of Coartem has been confirmed in many different patient populations around the world, consistently achieving 28-day [[polymerase chain reaction]]-corrected cure rates of >95% in the evaluable population, rapidly clearing parasitaemia and fever, and demonstrating a significant gametocidal effect, even in areas of widespread [[parasite]] resistance to other [[Antimalarial drug|antimalarials]].<ref>{{cite journal |author=Makanga M, Krudsood S |year=2009 |title=The clinical efficacy of artemether/lumefantrine (Coartem®) |journal=Malar J. |volume=8 |issue=1 |pages=S5 |pmid=19818172 |pmc=2760240 |doi=10.1186/1475-2875-8-S1-S5 |url=http://www.malariajournal.com/content/8%20Suppl%201//S5}}</ref> Coartem is much more effective than [[quinine]], the classical [[antimalarial]]. Randomised clinical trial in [[Uganda]] shows cure rate of [[malaria]] as high as 96% in the Coartem-treated group compared with 64% for the [[quinine]] group.<ref>{{cite journal |author=Achan J, Tibenderana JK, Kyabayinze D, Wabwire Mangen F, Kamya MR, Dorsey G, D'Alessandro U, Rosenthal PJ, Talisuna AO |year=2009 |title=Effectiveness of quinine versus artemether-lumefantrine for treating uncomplicated falciparum malaria in Ugandan children: randomised trial |journal=BMJ |volume=339 |issue= |pages=b2763 |pmid=19622553 |pmc=2714631 |doi=10.1136/bmj.b2763 |url=http://ukpmc.ac.uk/articlerender.cgi?artid=1785774}}</ref> For ''[[Plasmodium vivax]]'' infection, combination with [[piperaquine]] is more effective than Coartem.<ref>{{cite journal |author=Sinclair D, Zani B, Donegan S, Olliaro P, Garner P |year=2009 |title=Artemisinin-based combination therapy for treating uncomplicated malaria |journal=Cochrane Database Syst Rev. |volume=8 |issue=3 |pages=CD007483 |pmid=19588433 |doi=10.1002/14651858.CD007483.pub2 |editor1-last=Sinclair |editor1-first=David}}</ref>

Artemether has been assigned to category C by the FDA on the basis of animal data which shows an association with fetal-loss and deformity. However, clinical data appears to show that artemether is safe in pregnancy. A meta-analysis of 14 clinical trials that looked at artemether use in a total of 945 pregnant women did not find evidence of harm,<ref>{{cite journal|author=Dellicour S, Hall S, Chandramohan D, Greenwood B|title=The safety of artemisinins during pregnancy: a pressing question|journal=Malaria J|year= 2007|volume=6|pages=15|doi=10.1186/1475-2875-6-15}}</ref> and a clinical trial of artemether-lumefantrine designed to look at this question found fewer adverse events in the 138 pregnant women treated with artemther-lumefantrine than women treated with quinine.<ref>{{cite journal|author=Piola P, Nabasumba C, Turyakira E, ''et al.''|title=Efficacy and safety of artemether—lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial|journal=Lancet Infect Dis|volume=10|issue=11|pages=762&ndash;769|year=2010|doi=10.1016/S1473-3099(10)70202-4}}</ref>

===Anthelmintic===

During early 1980s [[China|Chinese]] scientists, by serendipity, discovered that artemether was not only an [[antimalarial|antimalarial agent]], but also effective against the [[schistosoma|blood flukes]]. Eventually, laboratory experiments have confirmed the broad spectrum of activity against different [[trematodes]], including all [[schistosoma|human schistosomes]], ''[[Clonorchis sinensis]]'', ''[[Fasciola hepatica]]'' and ''[[Opisthorchis viverrini]]''.<ref>{{cite journal |doi=10.1097/QCO.0b013e3282f19ec4 |author=Keiser J, Utzinger J |year=2007 |title=Artemisinins and synthetic trioxolanes in the treatment of helminth infections |journal=Curr Opin Infect Dis |volume=20 |issue=6 |pages=605–612 |pmid=17975411}}</ref> These studies revealed that artemether exhibits the highest activity against juvenile stages of the [[trematodes]], while adult worms are significantly less susceptible. In addition, there are no indication of [[neurotoxicity]] following repeated high doses. [[randomised control trial|Randomized controlled clinical trials]] confirmed that artemether, orally administered at a dose of 6&nbsp;mg/kg once every 2–3 weeks, results in no drug-related adverse effects, and significantly reduces the incidence and intensity of [[schistosome]] infections, including those of ''[[schistosoma mansoni|Scistosoma mansoni]]'', ''[[schistosoma japonicum|S. japonicum]]'' and ''[[schistosoma haematobium|S. haematobium]]''.<ref>{{cite journal |doi=10.1016/S0001-706X(02)00009-8 |author=Xiao S, Tanner M, N'Goran EK, Utzinger J, Chollet J, Bergquist R, Chen M, Zheng J |year=2002 |title=Recent investigations of artemether, a novel agent for the prevention of schistosomiasis japonica, mansoni and haematobia |journal=Acta Trop |volume=82 |issue=2 |pages=175–181 |pmid=12020890}}</ref><ref>{{cite journal |doi=10.2471/BLT.08.053041 |author=Hou XY, McManus DP, Gray DJ, Balen J, Luo XS, He YK, Ellis M, Williams GM, Li YS |year=2008 |title=A randomized, double-blind, placebo-controlled trial of safety and efficacy of combined praziquantel and artemether treatment for acute schistosomiasis japonica in China |journal=Bull World Health Organ |volume=86 |issue=10 |pages=788–795 |pmid=18949216 |pmc=2649525 |url=http://www.scielosp.org/scielo.php?script=sci_arttext&pid=S0042-96862008001000015&lng=en&nrm=iso&tlng=en}}</ref>

===Anticancer===

Artemether has been shown to have significant anticancer and [[antitumor]] activities. It is demonstrated that artemether caused strong inhibitory effects on [[glioma|brain glioma]] growth and [[angiogenesis]] in [[rat]]s.<ref>{{cite journal |doi=10.1177/1534735408330714 |author=Wu ZP, Gao CW, Wu YG, Zhu QS, Yan Chen, Xin Liu, Chuen Liu |year=2009 |title=Inhibitive effect of artemether on tumor growth and angiogenesis in the rat C6 orthotopic brain gliomas model |journal=Integr Cancer Ther |volume=8 |issue=1 |pages=88–92 |pmid=19174507 |url=http://ict.sagepub.com/cgi/pmidlookup?view=long&pmid=19174507}}</ref> It exhibits a dose- and time-dependent [[cytotoxicity]], and induced [[apoptosis]] and [[cell cycle|G2 cell cycle]] arrest in ovarian cancer cell lines,<ref>{{cite journal |author=Jiao Y, Ge CM, Meng QH, Cao JP, Tong J, Fan SJ |year=2007 |title=Dihydroartemisinin is an inhibitor of ovarian cancer cell growth |journal=Acta Pharmacol Sin |volume=8 |issue=7 |pages=1045–1056 |pmid=17588342 |doi=10.1111/j.1745-7254.2007.00612.x |url=http://www.chinaphar.com/1671-4083/28/1045.htm}}</ref> [[hl-60|human leukemia HL60 cells]],<ref>{{cite journal |doi=10.1097/CAD.0b013e3282f3f152 |author=Zhou HJ, Wang Z, Li A |year=2008 |title=Dihydroartemisinin induces apoptosis in human leukemia cells HL60 via downregulation of transferrin receptor expression |journal=Anticancer Drugs |volume=19 |issue=3 |pages=247–255 |pmid=18510170}}</ref> and human pancreatic cancer BxPC-3 and AsPC-1 cells.<ref>{{cite journal |author=Chen H, Sun B, Pan S, Jiang H, Sun X |year=2009 |title=Dihydroartemisinin induces apoptosis in human leukemia cells HL60 via downregulation of transferrin receptor expression |journal=Anticancer Drugs |volume=20 |issue=2 |pages=131–140 |pmid=19209030 |doi=10.1097/CAD.0b013e3283212ade}}</ref>

==Reference==

{{Reflist}}

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