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Pathway Description
Artemether Action Pathway (New)
Homo sapiens
Drug Action Pathway
Artemether is used to treat malaria usually in combination with lumefantrine in order to achieve greater efficacy in treatment. Artemether can be taken in a tablet or intramuscular injection, once administered into the body it has a rapid onset and is metabolized into an active metabolite dihydroartemisinin (DHA). DHA then enters the malaria cell and into the vacuole where it interacts with heme (a byproduct of hemoglobin) and creating cytotoxic radical species. This hinders growth and halts parasitic growth by damaging the food vacuole. This eventually causes cell death.
Food can be taken to help increase absorption, although grapefruit products should be avoided as they inhibit CYP450 3A4. If CYP450 3A4 is inhibited this reduces the clearance of artemether, leading to excessive plasma concentrations of artemether which can cause cardiovascular complications. DHA is then broken down by glucuronosyltransferases through glucuronidation so that it can become an inactive metabolite that is then excreted through bile.
References
Artemether Pathway (New) References
Abamecha A, Yilma D, Adissu W, Yewhalaw D, Abdissa A: Efficacy and safety of artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Ethiopia: a systematic review and meta-analysis. Malar J. 2021 May 6;20(1):213. doi: 10.1186/s12936-021-03745-8.
Pubmed: 33957925
Stover KR, King ST, Robinson J: Artemether-lumefantrine: an option for malaria. Ann Pharmacother. 2012 Apr;46(4):567-77. doi: 10.1345/aph.1Q539. Epub 2012 Apr 10.
Pubmed: 22496476
Silva-Pinto A, Domingos J, Cardoso M, Reis A, Benavente ED, Caldas JP, Conceicao C, Toscano C, Baptista-Fernandes T, Clark TG, Mansinho K, Campino S, Nogueira F: Artemether-lumefantrine treatment failure of uncomplicated Plasmodium falciparum malaria in travellers coming from Angola and Mozambique. Int J Infect Dis. 2021 Sep;110:151-154. doi: 10.1016/j.ijid.2021.07.008. Epub 2021 Jul 7.
Pubmed: 34242769
Makanga M, Krudsood S: The clinical efficacy of artemether/lumefantrine (Coartem). Malar J. 2009 Oct 12;8 Suppl 1(Suppl 1):S5. doi: 10.1186/1475-2875-8-S1-S5.
Pubmed: 19818172
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