Lumefantrine

Last updated
Lumefantrine
Lumefantrine.svg
Clinical data
AHFS/Drugs.com International Drug Names
MedlinePlus a609024
Routes of
administration
Oral
ATC code
Legal status
Legal status
  • US:C
Identifiers
  • 2-(Dibutylamino)-1-[(9Z)-2,7-dichloro-9-(4-chlorobenzylidene)-9H-fluoren-4-yl]ethanol
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.133.797 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C30H32Cl3NO
Molar mass 528.94 g·mol−1
3D model (JSmol)
Melting point 130 to 132 °C (266 to 270 °F)
  • Clc1ccc(cc1)\C=C3\c4c(c2c(cc(Cl)cc23)C(O)CN(CCCC)CCCC)ccc(Cl)c4
  • InChI=1S/C30H32Cl3NO/c1-3-5-13-34(14-6-4-2)19-29(35)28-18-23(33)17-27-25(15-20-7-9-21(31)10-8-20)26-16-22(32)11-12-24(26)30(27)28/h7-12,15-18,29,35H,3-6,13-14,19H2,1-2H3/b25-15- Yes check.svgY
  • Key:DYLGFOYVTXJFJP-MYYYXRDXSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Lumefantrine (or benflumetol) is an antimalarial drug. It is only used in combination with artemether. The term "co-artemether" is sometimes used to describe this combination. [1] Lumefantrine has a much longer half-life compared to artemether, and is therefore thought to clear any residual parasites that remain after combination treatment. [2]

Lumefantrine, along with pyronaridine and naphtoquine, were synthesized during the Chinese Project 523 antimalaria drug research effort initiated in 1967; these compounds are all used in combination antimalaria therapies. [3] [4] [5]

See also

Related Research Articles

<span class="mw-page-title-main">Malaria</span> Mosquito-borne infectious disease

Malaria is a mosquito-borne infectious disease that affects humans and other vertebrates. Human malaria causes symptoms that typically include fever, fatigue, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. Symptoms usually begin 10 to 15 days after being bitten by an infected Anopheles mosquito. If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria.

Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young children and pregnant women. As of 2018, modern treatments, including for severe malaria, continued to depend on therapies deriving historically from quinine and artesunate, both parenteral (injectable) drugs, expanding from there into the many classes of available modern drugs. Incidence and distribution of the disease is expected to remain high, globally, for many years to come; moreover, known antimalarial drugs have repeatedly been observed to elicit resistance in the malaria parasite—including for combination therapies featuring artemisinin, a drug of last resort, where resistance has now been observed in Southeast Asia. As such, the needs for new antimalarial agents and new strategies of treatment remain important priorities in tropical medicine. As well, despite very positive outcomes from many modern treatments, serious side effects can impact some individuals taking standard doses.

<i>Artemisia annua</i> Herb known as sweet wormwood used to treat malaria

Artemisia annua, also known as sweet wormwood, sweet annie, sweet sagewort, annual mugwort or annual wormwood, is a common type of wormwood native to temperate Asia, but naturalized in many countries including scattered parts of North America.

<span class="mw-page-title-main">Artemisinin</span> Group of drugs used against malaria

Artemisinin and its semisynthetic derivatives are a group of drugs used in the treatment of malaria due to Plasmodium falciparum. It was discovered in 1972 by Tu Youyou, who shared the 2015 Nobel Prize in Physiology or Medicine for her discovery. Artemisinin-based combination therapies (ACTs) are now standard treatment worldwide for P. falciparum malaria as well as malaria due to other species of Plasmodium. Artemisinin is extracted from the plant Artemisia annua a herb employed in Chinese traditional medicine. A precursor compound can be produced using a genetically engineered yeast, which is much more efficient than using the plant.

<span class="mw-page-title-main">Artemether</span> Chemical compound

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

<span class="mw-page-title-main">Artesunate</span> Chemical compound

Artesunate (AS) is a medication used to treat malaria. The intravenous form is preferred to quinine for severe malaria. Often it is used as part of combination therapy, such as artesunate plus mefloquine. It is not used for the prevention of malaria. Artesunate can be given by injection into a vein, injection into a muscle, by mouth, and by rectum.

Combination therapy or polytherapy is therapy that uses more than one medication or modality. Typically, the term refers to using multiple therapies to treat a single disease, and often all the therapies are pharmaceutical. 'Pharmaceutical' combination therapy may be achieved by prescribing/administering separate drugs, or, where available, dosage forms that contain more than one active ingredient.

<span class="mw-page-title-main">Piperacillin</span> Antibiotic medication

Piperacillin is a broad-spectrum β-lactam antibiotic of the ureidopenicillin class. The chemical structure of piperacillin and other ureidopenicillins incorporates a polar side chain that enhances penetration into Gram-negative bacteria and reduces susceptibility to cleavage by Gram-negative beta lactamase enzymes. These properties confer activity against the important hospital pathogen Pseudomonas aeruginosa. Thus piperacillin is sometimes referred to as an "anti-pseudomonal penicillin".

Artemether/lumefantrine, sold under the trade name Coartem among others, is a combination of the two medications artemether and lumefantrine. It is used to treat malaria caused by Plasmodium falciparum that is not treatable with chloroquine. It is not typically used to prevent malaria. It is taken by mouth.

Chlorproguanil/dapsone/artesunate was an experimental antimalarial treatment that entered Phase III clinical trials in 2006. Development was halted because it was associated with an increased risk of haemolytic anaemia in patients with glucose-6-phosphate dehydrogenase deficiency.

<span class="mw-page-title-main">Dihydroartemisinin</span> Drug used to treat malaria

Dihydroartemisinin is a drug used to treat malaria. Dihydroartemisinin is the active metabolite of all artemisinin compounds and is also available as a drug in itself. It is a semi-synthetic derivative of artemisinin and is widely used as an intermediate in the preparation of other artemisinin-derived antimalarial drugs. It is sold commercially in combination with piperaquine and has been shown to be equivalent to artemether/lumefantrine.

<span class="mw-page-title-main">Amodiaquine</span> Chemical compound

Amodiaquine (ADQ) is a medication used to treat malaria, including Plasmodium falciparum malaria when uncomplicated. It is recommended to be given with artesunate to reduce the risk of resistance. Due to the risk of rare but serious side effects, it is not generally recommended to prevent malaria. Though, the World Health Organization (WHO) in 2013 recommended use for seasonal preventive in children at high risk in combination with sulfadoxine and pyrimethamine.

Artesunate/amodiaquine, sold under the trade name Camoquin among others, is a medication used for the treatment of malaria. It is a fixed-dose combination of artesunate and amodiaquine. Specifically it recommended for acute uncomplicated Plasmodium falciparum malaria. It is taken by mouth.

<span class="mw-page-title-main">Pyronaridine</span> Chemical compound

Pyronaridine is an antimalarial drug. It was first made in 1970 and has been in clinical use in China since the 1980s.

<span class="mw-page-title-main">Piperaquine</span> Chemical compound

Piperaquine is an antiparasitic drug used in combination with dihydroartemisinin to treat malaria. Piperaquine was developed under the Chinese National Malaria Elimination Programme in the 1960s and was adopted throughout China as a replacement for the structurally similar antimalarial drug chloroquine. Due to widespread parasite resistance to piperaquine, the drug fell out of use as a monotherapy, and is instead used as a partner drug for artemisinin combination therapy. Piperaquine kills parasites by disrupting the detoxification of host heme.

Project 523 is a code name for a 1967 secret military project of the People's Republic of China to find antimalarial medications. Named after the date the project launched, 23 May, it addressed malaria, an important threat in the Vietnam War. At the behest of Ho Chi Minh, Prime Minister of North Vietnam, Zhou Enlai, the Premier of the People's Republic of China, convinced Mao Zedong, Chairman of the Chinese Communist Party, to start the mass project "to keep [the] allies' troops combat-ready", as the meeting minutes put it. More than 500 Chinese scientists were recruited. The project was divided into three streams. The one for investigating traditional Chinese medicine discovered and led to the development of a class of new antimalarial drugs called artemisinins. Launched during and lasting throughout the Cultural Revolution, Project 523 was officially terminated in 1981.

<span class="mw-page-title-main">Tu Youyou</span> Chinese pharmaceutical chemist

Tu Youyou is a Chinese malariologist and pharmaceutical chemist. She discovered artemisinin and dihydroartemisinin, used to treat malaria, a breakthrough in twentieth-century tropical medicine, saving millions of lives in South China, Southeast Asia, Africa, and South America.

Zhou Yiqing is a professor of medicine at the Institute of Microbiology and Epidemiology of the People's Liberation Army Academy of Military Medical Sciences. He was one of the scientists who participated in the Project 523 of the Chinese Government under Chairman Mao Zedong. The project resulted in the discovery of artemisinins, a class of antimalarial drugs, from the medicinal plant Artemisia annua.

Artesunate/pyronaridine, sold under the brand name Pyramax, is a fixed-dose combination medication for the treatment of malaria. It can be used for malaria of both the P. falciparum and P. vivax types. It combines artesunate and pyronaridine. It is taken by mouth.

Grace Olusola Gbotosho is a Nigerian pharmacologist who specialises in the pharmacodynamics and pharmacokinetics of antimalarial medication. She is a senior lecturer at the University of Ibadan College of Medicine's Department of Pharmacology and Therapeutics.

References

  1. Toovey S, Jamieson A, Nettleton G (August 2003). "Successful co-artemether (artemether-lumefantrine) clearance of falciparum malaria in a patient with severe cholera in Mozambique". Travel Medicine and Infectious Disease. 1 (3): 177–179. doi:10.1016/j.tmaid.2003.09.002. PMID   17291911.
  2. White NJ, van Vugt M, Ezzet F (August 1999). "Clinical pharmacokinetics and pharmacodynamics and pharmacodynamics of artemether-lumefantrine". Clinical Pharmacokinetics. 37 (2): 105–125. doi:10.2165/00003088-199937020-00002. PMID   10496300. S2CID   72714420.
  3. Cui L, Su XZ (October 2009). "Discovery, mechanisms of action and combination therapy of artemisinin". Expert Review of Anti-Infective Therapy. 7 (8): 999–1013. doi:10.1586/eri.09.68. PMC   2778258 . PMID   19803708.
  4. Benjamin J, Moore B, Lee ST, Senn M, Griffin S, Lautu D, et al. (May 2012). "Artemisinin-naphthoquine combination therapy for uncomplicated pediatric malaria: a tolerability, safety, and preliminary efficacy study". Antimicrobial Agents and Chemotherapy. 56 (5): 2465–2471. doi:10.1128/AAC.06248-11. PMC   3346652 . PMID   22330921.
  5. Laman M, Moore BR, Benjamin JM, Yadi G, Bona C, Warrel J, et al. (December 2014). "Artemisinin-naphthoquine versus artemether-lumefantrine for uncomplicated malaria in Papua New Guinean children: an open-label randomized trial". PLOS Medicine. 11 (12): e1001773. doi: 10.1371/journal.pmed.1001773 . PMC   4280121 . PMID   25549086.