Artesunate
Encyclopedia
Artesunate is part of the artemisinin
group of drugs that treat malaria. It is a semi-synthetic derivative of artemisinin that is water-soluble and may therefore be given by injection. It is sometimes abbreviated AS.
; it has also been shown to be >90% efficacious at reducing egg production in Schistosoma haematobium
infection.
According to WHO
intravenous AS is the drug of choice for severe malaria both in children and adults where there is low transmission. In regions where transmission is high, randomized trials among Asian adults and African children strongly advocates the use of artesunate over quinine as the treatment of choice for falciparum malaria.
or UK
. In the UK, artesunate is available on a named patient basis only.
Intravenous dose of IV artesunate for treatment of severe malaria:
Artesunate must always be given with another antimalarial such as mefloquine
or amodiaquine
so as to avoid the development of resistance. The combination of artesunate/amodiaquine has been found to be equivalent to co-artemether
.
For severe malaria during pregnancy, the WHO recommends artesunate or quinine during the first trimester and artesunate as the first-line therapy during the second and third trimesters.
(DHA) by reacting it with succinic acid anhydride in basic medium. Pyridine
as base/solvent, sodium bicarbonate
in chloroform and catalyst DMAP
(N,N-dimethylaminopyridine) and triethylamine
in 1,2-dichloroethane have been used, with yields of up to 100%. A large scale process involves treatment of DHA in dichloromethane
with a mixture of pyridine, a catalytic amount of DMAP and succinic anhydride. The dichloromethane mixture is stirred for 6–9 h to get artesunate in quantitative yield. The product is further re-crystallized from dichloromethane. alpha-Artesunate is exclusively formed (m.p 135–137˚C).
Artemisinin
Artemisinin , also known as Qinghaosu , and its derivatives are a group of drugs that possess the most rapid action of all current drugs against falciparum malaria. Treatments containing an artemisinin derivative are now standard treatment worldwide for falciparum malaria...
group of drugs that treat malaria. It is a semi-synthetic derivative of artemisinin that is water-soluble and may therefore be given by injection. It is sometimes abbreviated AS.
Uses
Artesunate is used primarily as treatment for malariaMalaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
; it has also been shown to be >90% efficacious at reducing egg production in Schistosoma haematobium
Schistosoma haematobium
Schistosoma haematobium is an important digenetic trematode, and is found in the Middle East, India, Portugal and Africa. It is a major agent of schistosomiasis; more specifically, it is associated with urinary schistosomiasis....
infection.
According to WHO
Who
Who may refer to:* Who , an English-language pronoun* who , a Unix command* Who?, one of the Five Ws in journalism- Art and entertainment :* Who? , a 1958 novel by Algis Budrys...
intravenous AS is the drug of choice for severe malaria both in children and adults where there is low transmission. In regions where transmission is high, randomized trials among Asian adults and African children strongly advocates the use of artesunate over quinine as the treatment of choice for falciparum malaria.
Dosing
There are no licensed forms of artesunate available in the U.S.United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
or UK
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
. In the UK, artesunate is available on a named patient basis only.
Intravenous dose of IV artesunate for treatment of severe malaria:
- 2.4 mg/kg loading dose over 5 minutes
- 2.4 mg/kg dose 12 hours later
- 2.4 mg/kg once daily after that
Artesunate must always be given with another antimalarial such as mefloquine
Mefloquine
Mefloquine hydrochloride is an orally administered medication used in the prevention and treatment of malaria. Mefloquine was developed in the 1970s at the United States Department of Defense's Walter Reed Army Institute of Research as a synthetic analogue of quinine...
or amodiaquine
Amodiaquine
Amodiaquine is a 4-aminoquinoline compound related to chloroquine, used as an antimalarial and anti-inflammatory agent....
so as to avoid the development of resistance. The combination of artesunate/amodiaquine has been found to be equivalent to co-artemether
Artemether
Artemether is an antimalarial for the treatment of multi-drug resistant strains of falciparum malaria. It is combined with Lumefantrine and sold by Novartis under the brand names Riamet and Co-Artem.-Chemical nature:...
.
For severe malaria during pregnancy, the WHO recommends artesunate or quinine during the first trimester and artesunate as the first-line therapy during the second and third trimesters.
Synthesis
Artesunate is prepared from dihydroartemisininDihydroartemisinin
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...
(DHA) by reacting it with succinic acid anhydride in basic medium. Pyridine
Pyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one C-H group replaced by a nitrogen atom...
as base/solvent, sodium bicarbonate
Sodium bicarbonate
Sodium bicarbonate or sodium hydrogen carbonate is the chemical compound with the formula Na HCO3. Sodium bicarbonate is a white solid that is crystalline but often appears as a fine powder. It has a slightly salty, alkaline taste resembling that of washing soda . The natural mineral form is...
in chloroform and catalyst DMAP
4-Dimethylaminopyridine
4-Dimethylaminopyridine is a derivative of pyridine with the chemical formula 2NC5H4N. This colourless solid is a useful nucleophilic catalyst for a variety of reactions such as esterifications with anhydrides, the Baylis-Hillman reaction, hydrosilylations, tritylation, the Steglich...
(N,N-dimethylaminopyridine) and triethylamine
Triethylamine
Triethylamine is the chemical compound with the formula N3, commonly abbreviated Et3N. It is also abbreviated TEA, yet this abbreviation must be used carefully to avoid confusion with triethanolamine, for which TEA is also a common abbreviation....
in 1,2-dichloroethane have been used, with yields of up to 100%. A large scale process involves treatment of DHA in dichloromethane
Dichloromethane
Dichloromethane is an organic compound with the formula CH2Cl2. This colorless, volatile liquid with a moderately sweet aroma is widely used as a solvent. Although it is not miscible with water, it is miscible with many organic solvents...
with a mixture of pyridine, a catalytic amount of DMAP and succinic anhydride. The dichloromethane mixture is stirred for 6–9 h to get artesunate in quantitative yield. The product is further re-crystallized from dichloromethane. alpha-Artesunate is exclusively formed (m.p 135–137˚C).