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Artemether

April 12, 2024

Artemether is a medication used for the treatment of malaria.[1][2] The injectable form is specifically used for severe malaria rather than quinine.[2] In adults, it may not be as effective as artesunate.[2] It is given by injection in a muscle.[2] It is also available by mouth in combination with lumefantrine, known as artemether/lumefantrine.[1][3]

Artemether
Clinical data
Trade namesMany[1]
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Intramuscular[2] Oral
ATC code
Legal status
Legal status
  • UK: POM (Prescription only)
  • In general: ℞ (Prescription only)
Identifiers
  • (3R,5aS,6R,8aS,9R,10S,12R,12aR)-10-methoxy-3,6,9-trimethyldecahydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]-2-benzopyran
CAS Number
  • 71963-77-4 Y
PubChem CID
  • 68911
DrugBank
  • DB06697 Y
ChemSpider
  • 62138 Y
UNII
  • C7D6T3H22J
KEGG
  • D02483 Y
ChEBI
  • CHEBI:195280 Y
PDB ligand
  • D8Z (PDBe, RCSB PDB)
CompTox Dashboard (EPA)
  • DTXSID7040651
ECHA InfoCard100.189.847
Chemical and physical data
FormulaC16H26O5
Molar mass298.379 g·mol−1
3D model (JSmol)
  • Interactive image
Melting point86 to 88 °C (187 to 190 °F)
  • C[C@@H]1CC[C@@H]3C42OO[C@](C)(CC[C@@H]12)O[C@H]4O[C@H](OC)[C@@H]3C
  • 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 Y
  • Key:SXYIRMFQILZOAM-HVNFFKDJSA-N Y
 NY (what is this?)  (verify)

Artemether causes relatively few side effects.[4] An irregular heartbeat may rarely occur.[4] While there is evidence that use during pregnancy may be harmful in animals, there is no evidence of concern in humans.[4] The World Health Organization (WHO) therefore recommends its use during pregnancy.[4] It is in the artemisinin class of medication.[4]

Artemether has been studied since at least 1981, and has been in medical use since 1987.[5] It is on the World Health Organization's List of Essential Medicines.[6]

Medical uses edit

Artemether is an antimalarial drug for uncomplicated malaria caused by  P. falciparum (and chloroquine-resistant P. falciparum) or chloroquine-resistant P. vivax parasites.[1][7] Artemether can also be used to treat severe malaria.[2]

The World Health Organization (WHO) recommends the treatment of uncomplicated P. falciparum with artemisinin-based combination therapy.[8] Given in combination with lumefantrine, it may be followed by a 14-day regimen of primaquine to prevent relapse of P. vivax or P. ovale malarial parasites and provide a complete cure.[9]

Artemether can also be used in treating and preventing trematode infections of schistosomiasis when used in combination with praziquantel.[10]

Artemether is rated category C by the FDA based on animal studies where artemisinin derivatives have shown an association with fetal loss and deformity. Some studies, however, do not show evidence of harm.[11][12]

Side effects edit

Possible side effects include cardiac effects such as bradycardia and QT interval prolongation.[1][13] Also, possible central nervous system toxicity has been shown in animal studies.[14][15]

Drug interactions edit

Plasma artemether level was found to be lower when the combination product was used with lopinavir/ritonavir.[15] There is also decreased drug exposure associated with concurrent use with efavirenz or nevirapine.[16][17]

Artemether/lumefantrine should not be used with drugs that inhibit CYP3A4.[1][18]

Hormonal contraceptives may not be as efficacious when used with artemether/lumefantrine.[18]

Pharmacology edit

Mechanism of action edit

A possible mechanism of action is that artemisinin drugs exert their cidal action by inhibiting PfATP6. Since PfATP6 is an enzyme regulating cellular calcium concentration, its malfunctioning will lead to intracellular calcium accumulation, which in turns causes cell death.[19]

Pharmacokinetics edit

Absorption of artemether is improved 2- to 3-fold with food. It is highly bound to protein (95.4%). Peak concentrations of artemether are seen 2 hours after administration.[3]

Artemether is metabolized in the human body to the active metabolite, dihydroartemisinin, primarily by hepatic enzymes CYP3A4/5.[3] Both the parent drug and active metabolite are eliminated with a half-life of about 2 hours.[3]

Chemistry edit

Artemether is a methyl ether derivative of artemisinin, which is a peroxide-containing lactone isolated from the antimalarial plant Artemisia annua. It is also known as dihydroartemisinin methyl ether, but its 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. It is a relatively lipophilic and unstable drug,[20] which acts by creating reactive free radicals in addition to affecting the membrane transport system of the plasmodium organism.[13]

References edit

  1. ^ a b c d e f "Artemether and Lumefantrine (Monograph)". Drugs.com. 22 February 2023. Retrieved 17 February 2024.
  2. ^ a b c d e f Esu EB, Effa EE, Opie ON, Meremikwu MM (June 2019). "Artemether for severe malaria". The Cochrane Database of Systematic Reviews. 6 (6): CD010678. doi:10.1002/14651858.CD010678.pub3. PMC 6580442. PMID 31210357.
  3. ^ a b c d "Coartem- artemether and lumefantrine tablet". DailyMed. 5 August 2019. Retrieved 26 April 2020.
  4. ^ a b c d e Kovacs SD, Rijken MJ, Stergachis A (February 2015). "Treating severe malaria in pregnancy: a review of the evidence". Drug Safety. 38 (2): 165–181. doi:10.1007/s40264-014-0261-9. PMC 4328128. PMID 25556421.
  5. ^ Rao Y, Zhang D, Li R (2016). Tu Youyou and the Discovery of Artemisinin: 2015 Nobel Laureate in Physiology or Medicine. World Scientific. p. 162. ISBN 9789813109919. from the original on 2017-09-10.
  6. ^ World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. 2019. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  7. ^ Makanga M, Krudsood S (October 2009). "The clinical efficacy of artemether/lumefantrine (Coartem)". Malaria Journal. 8 (Suppl 1): S5. doi:10.1186/1475-2875-8-S1-S5. PMC 2760240. PMID 19818172.
  8. ^ Treatment of Uncomplicated Plasmodium falciparum Malaria. World Health Organization. 2015-01-01. from the original on 2017-09-10.
  9. ^ Treatment Of Uncomplicated Malaria Caused By P. vivax, P. ovale, P. malariae or P. knowlesi. World Health Organization. 2015-01-01. from the original on 2017-09-10.
  10. ^ Pérez del Villar L, Burguillo FJ, López-Abán J, Muro A (2012-01-01). "Systematic review and meta-analysis of artemisinin based therapies for the treatment and prevention of schistosomiasis". PLOS ONE. 7 (9): e45867. Bibcode:2012PLoSO...745867P. doi:10.1371/journal.pone.0045867. PMC 3448694. PMID 23029285.
  11. ^ Dellicour S, Hall S, Chandramohan D, Greenwood B (February 2007). "The safety of artemisinins during pregnancy: a pressing question". Malaria Journal. 6: 15. doi:10.1186/1475-2875-6-15. PMC 1802871. PMID 17300719.
  12. ^ Piola P, Nabasumba C, Turyakira E, Dhorda M, Lindegardh N, Nyehangane D, et al. (November 2010). "Efficacy and safety of artemether-lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial". The Lancet. Infectious Diseases. 10 (11): 762–769. doi:10.1016/S1473-3099(10)70202-4. hdl:10144/116337. PMID 20932805.
  13. ^ a b "Artemether". www.antimicrobe.org. from the original on 2017-02-23. Retrieved 2016-11-09.
  14. ^ . apps.who.int. Archived from the original on 2016-11-10. Retrieved 2016-11-09.
  15. ^ a b Askling HH, Bruneel F, Burchard G, Castelli F, Chiodini PL, Grobusch MP, et al. (September 2012). "Management of imported malaria in Europe". Malaria Journal. 11: 328. doi:10.1186/1475-2875-11-328. PMC 3489857. PMID 22985344.
  16. ^ Van Geertruyden JP (April 2014). "Interactions between malaria and human immunodeficiency virus anno 2014". Clinical Microbiology and Infection. 20 (4): 278–285. doi:10.1111/1469-0691.12597. PMC 4368411. PMID 24528518.
  17. ^ Kiang TK, Wilby KJ, Ensom MH (February 2014). "Clinical pharmacokinetic drug interactions associated with artemisinin derivatives and HIV-antivirals". Clinical Pharmacokinetics. 53 (2): 141–153. doi:10.1007/s40262-013-0110-5. PMID 24158666. S2CID 1281113.
  18. ^ a b Stover KR, King ST, Robinson J (April 2012). "Artemether-lumefantrine: an option for malaria". The Annals of Pharmacotherapy. 46 (4): 567–577. doi:10.1345/aph.1Q539. PMID 22496476. S2CID 7678606.
  19. ^ Guo Z (March 2016). "Artemisinin anti-malarial drugs in China". Acta Pharmaceutica Sinica. B. 6 (2): 115–124. doi:10.1016/j.apsb.2016.01.008. PMC 4788711. PMID 27006895.
  20. ^ De Spiegeleer BM, D'Hondt M, Vangheluwe E, Vandercruyssen K, De Spiegeleer BV, Jansen H, et al. (November 2012). "Relative response factor determination of β-artemether degradants by a dry heat stress approach". Journal of Pharmaceutical and Biomedical Analysis. 70: 111–116. doi:10.1016/j.jpba.2012.06.002. hdl:1854/LU-2938963. PMID 22770733.

April 12, 2024
artemether, medication, used, treatment, malaria, injectable, form, specifically, used, severe, malaria, rather, than, quinine, adults, effective, artesunate, given, injection, muscle, also, available, mouth, combination, with, lumefantrine, known, artemether,. Artemether is a medication used for the treatment of malaria 1 2 The injectable form is specifically used for severe malaria rather than quinine 2 In adults it may not be as effective as artesunate 2 It is given by injection in a muscle 2 It is also available by mouth in combination with lumefantrine known as artemether lumefantrine 1 3 ArtemetherClinical dataTrade namesMany 1 AHFS Drugs comInternational Drug NamesRoutes ofadministrationIntramuscular 2 OralATC codeP01BE02 WHO Legal statusLegal statusUK POM Prescription only In general Prescription only IdentifiersIUPAC name 3R 5aS 6R 8aS 9R 10S 12R 12aR 10 methoxy 3 6 9 trimethyldecahydro 12H 3 12 epoxy 1 2 dioxepino 4 3 i 2 benzopyranCAS Number71963 77 4 YPubChem CID68911DrugBankDB06697 YChemSpider62138 YUNIIC7D6T3H22JKEGGD02483 YChEBICHEBI 195280 YPDB ligandD8Z PDBe RCSB PDB CompTox Dashboard EPA DTXSID7040651ECHA InfoCard100 189 847Chemical and physical dataFormulaC 16H 26O 5Molar mass298 379 g mol 13D model JSmol Interactive imageMelting point86 to 88 C 187 to 190 F SMILES C C H 1CC C H 3C42OO C C CC C H 12 O C H 4O C H OC C H 3CInChI 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 YKey SXYIRMFQILZOAM HVNFFKDJSA N Y N Y what is this verify Artemether causes relatively few side effects 4 An irregular heartbeat may rarely occur 4 While there is evidence that use during pregnancy may be harmful in animals there is no evidence of concern in humans 4 The World Health Organization WHO therefore recommends its use during pregnancy 4 It is in the artemisinin class of medication 4 Artemether has been studied since at least 1981 and has been in medical use since 1987 5 It is on the World Health Organization s List of Essential Medicines 6 Contents 1 Medical uses 2 Side effects 3 Drug interactions 4 Pharmacology 4 1 Mechanism of action 4 2 Pharmacokinetics 5 Chemistry 6 ReferencesMedical uses editArtemether is an antimalarial drug for uncomplicated malaria caused by P falciparum and chloroquine resistant P falciparum or chloroquine resistant P vivax parasites 1 7 Artemether can also be used to treat severe malaria 2 The World Health Organization WHO recommends the treatment of uncomplicated P falciparum with artemisinin based combination therapy 8 Given in combination with lumefantrine it may be followed by a 14 day regimen of primaquine to prevent relapse of P vivax or P ovale malarial parasites and provide a complete cure 9 Artemether can also be used in treating and preventing trematode infections of schistosomiasis when used in combination with praziquantel 10 Artemether is rated category C by the FDA based on animal studies where artemisinin derivatives have shown an association with fetal loss and deformity Some studies however do not show evidence of harm 11 12 Side effects editPossible side effects include cardiac effects such as bradycardia and QT interval prolongation 1 13 Also possible central nervous system toxicity has been shown in animal studies 14 15 Drug interactions editPlasma artemether level was found to be lower when the combination product was used with lopinavir ritonavir 15 There is also decreased drug exposure associated with concurrent use with efavirenz or nevirapine 16 17 Artemether lumefantrine should not be used with drugs that inhibit CYP3A4 1 18 Hormonal contraceptives may not be as efficacious when used with artemether lumefantrine 18 Pharmacology editMechanism of action edit A possible mechanism of action is that artemisinin drugs exert their cidal action by inhibiting PfATP6 Since PfATP6 is an enzyme regulating cellular calcium concentration its malfunctioning will lead to intracellular calcium accumulation which in turns causes cell death 19 Pharmacokinetics edit Absorption of artemether is improved 2 to 3 fold with food It is highly bound to protein 95 4 Peak concentrations of artemether are seen 2 hours after administration 3 Artemether is metabolized in the human body to the active metabolite dihydroartemisinin primarily by hepatic enzymes CYP3A4 5 3 Both the parent drug and active metabolite are eliminated with a half life of about 2 hours 3 Chemistry editArtemether is a methyl ether derivative of artemisinin which is a peroxide containing lactone isolated from the antimalarial plant Artemisia annua It is also known as dihydroartemisinin methyl ether but its 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 It is a relatively lipophilic and unstable drug 20 which acts by creating reactive free radicals in addition to affecting the membrane transport system of the plasmodium organism 13 References edit a b c d e f Artemether and Lumefantrine Monograph Drugs com 22 February 2023 Retrieved 17 February 2024 a b c d e f Esu EB Effa EE Opie ON Meremikwu MM June 2019 Artemether for severe malaria The Cochrane Database of Systematic Reviews 6 6 CD010678 doi 10 1002 14651858 CD010678 pub3 PMC 6580442 PMID 31210357 a b c d Coartem artemether and lumefantrine tablet DailyMed 5 August 2019 Retrieved 26 April 2020 a b c d e Kovacs SD Rijken MJ Stergachis A February 2015 Treating severe malaria in pregnancy a review of the evidence Drug Safety 38 2 165 181 doi 10 1007 s40264 014 0261 9 PMC 4328128 PMID 25556421 Rao Y Zhang D Li R 2016 Tu Youyou and the Discovery of Artemisinin 2015 Nobel Laureate in Physiology or Medicine World Scientific p 162 ISBN 9789813109919 Archived from the original on 2017 09 10 World Health Organization model list of essential medicines 21st list 2019 Geneva World Health Organization 2019 hdl 10665 325771 WHO MVP EMP IAU 2019 06 License CC BY NC SA 3 0 IGO Makanga M Krudsood S October 2009 The clinical efficacy of artemether lumefantrine Coartem Malaria Journal 8 Suppl 1 S5 doi 10 1186 1475 2875 8 S1 S5 PMC 2760240 PMID 19818172 Treatment of Uncomplicated Plasmodium falciparum Malaria World Health Organization 2015 01 01 Archived from the original on 2017 09 10 Treatment Of Uncomplicated Malaria Caused By P vivax P ovale P malariae or P knowlesi World Health Organization 2015 01 01 Archived from the original on 2017 09 10 Perez del Villar L Burguillo FJ Lopez Aban J Muro A 2012 01 01 Systematic review and meta analysis of artemisinin based therapies for the treatment and prevention of schistosomiasis PLOS ONE 7 9 e45867 Bibcode 2012PLoSO 745867P doi 10 1371 journal pone 0045867 PMC 3448694 PMID 23029285 Dellicour S Hall S Chandramohan D Greenwood B February 2007 The safety of artemisinins during pregnancy a pressing question Malaria Journal 6 15 doi 10 1186 1475 2875 6 15 PMC 1802871 PMID 17300719 Piola P Nabasumba C Turyakira E Dhorda M Lindegardh N Nyehangane D et al November 2010 Efficacy and safety of artemether lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria an open label randomised non inferiority trial The Lancet Infectious Diseases 10 11 762 769 doi 10 1016 S1473 3099 10 70202 4 hdl 10144 116337 PMID 20932805 a b Artemether www antimicrobe org Archived from the original on 2017 02 23 Retrieved 2016 11 09 WHO Model Prescribing Information Drugs Used in Parasitic Diseases Second Edition Protozoa Malaria Artemether apps who int Archived from the original on 2016 11 10 Retrieved 2016 11 09 a b Askling HH Bruneel F Burchard G Castelli F Chiodini PL Grobusch MP et al September 2012 Management of imported malaria in Europe Malaria Journal 11 328 doi 10 1186 1475 2875 11 328 PMC 3489857 PMID 22985344 Van Geertruyden JP April 2014 Interactions between malaria and human immunodeficiency virus anno 2014 Clinical Microbiology and Infection 20 4 278 285 doi 10 1111 1469 0691 12597 PMC 4368411 PMID 24528518 Kiang TK Wilby KJ Ensom MH February 2014 Clinical pharmacokinetic drug interactions associated with artemisinin derivatives and HIV antivirals Clinical Pharmacokinetics 53 2 141 153 doi 10 1007 s40262 013 0110 5 PMID 24158666 S2CID 1281113 a b Stover KR King ST Robinson J April 2012 Artemether lumefantrine an option for malaria The Annals of Pharmacotherapy 46 4 567 577 doi 10 1345 aph 1Q539 PMID 22496476 S2CID 7678606 Guo Z March 2016 Artemisinin anti malarial drugs in China Acta Pharmaceutica Sinica B 6 2 115 124 doi 10 1016 j apsb 2016 01 008 PMC 4788711 PMID 27006895 De Spiegeleer BM D Hondt M Vangheluwe E Vandercruyssen K De Spiegeleer BV Jansen H et al November 2012 Relative response factor determination of b artemether degradants by a dry heat stress approach Journal of Pharmaceutical and Biomedical Analysis 70 111 116 doi 10 1016 j jpba 2012 06 002 hdl 1854 LU 2938963 PMID 22770733 Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Artemether amp oldid 1208361260, wikipedia, wiki, book, books, library,

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