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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/12/17 17:13:00」(JST)
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Artesunate
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| Clinical data |
| AHFS/Drugs.com |
International Drug Names |
| Pregnancy cat. |
? |
| Legal status |
Not licensed in UK or US |
| Routes |
oral, IV, IM |
| Identifiers |
| CAS number |
88495-63-0 N
80155-81-3 (sodium salt) |
| ATC code |
P01BE03 |
| PubChem |
CID 5464098 |
| ChemSpider |
16735675 Y |
| UNII |
60W3249T9M Y |
| ChEMBL |
CHEMBL258608 N |
| NIAID ChemDB |
112081 |
| Chemical data |
| Formula |
C19H28O8 |
| Mol. mass |
384.421 g/mol |
SMILES
- [H][C@@]12CC[C@@]3(C)OO[C@@]11[C@@]([H])(CC[C@H]2C)[C@@H](C)[C@H](OC(=O)CCC(O)=O)O[C@]1([H])O3
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InChI
-
InChI=1S/C19H28O8/c1-10-4-5-13-11(2)16(23-15(22)7-6-14(20)21)24-17-19(13)12(10)8-9-18(3,25-17)26-27-19/h10-13,16-17H,4-9H2,1-3H3,(H,20,21)/t10-,11-,12+,13+,16-,17-,18-,19-/m1/s1 N
Key:FIHJKUPKCHIPAT-AHIGJZGOSA-N N
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| N (what is this?) (verify) |
Artesunate (INN) 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.
Contents
- 1 Uses
- 2 Dosing
- 3 Synthesis
- 4 Drug resistance
- 5 References
Uses[edit]
Artesunate is used primarily as treatment for malaria; it has also been shown to be >90% efficacious at reducing egg production in Schistosoma haematobium infection.[1]
According to the World Health Organization, intramuscular, intravenous, or intra-rectal artesunate is the first line treatment for severe malaria.[2] 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.[3][4]
Dosing[edit]
There are no licensed forms of artesunate available in the U.S. or UK. 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[5][6] or amodiaquine[7] to avoid the development of resistance. The combination of artesunate/amodiaquine has been found to be equivalent to co-artemether.[8]
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.[9]
Synthesis[edit]
Artesunate is prepared from dihydroartemisinin (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).
Drug resistance[edit]
Clinical evidence of drug resistance has appeared in Western Cambodia, where artemisinin monotherapy is common.[10] There are as yet no reports of resistance emerging elsewhere.
References[edit]
- ^ Boulangier D, Dieng Y, Cisse B, et al. (2007). "Antischistosomal efficacy of artesunate combination therapies administered as curative treatments for malaria attacks". Trans R Soc Trop Med Hyg 101 (2): 113–16. doi:10.1016/j.trstmh.2006.03.003. PMID 16765398.
- ^ WHO (2013). Overview of malaria treatment. World Health Organization, Geneva.
- ^ South East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT) (2005). "Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial". The Lancet 366 (9487): 717–725. doi:10.1016/S0140-6736(05)67176-0. PMID 16125588.
- ^ Dondorp AL, et al. (2010). "Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial". The Lancet 376 (9753): 1647–1657. doi:10.1016/S0140-6736(10)61924-1. PMC 3033534. PMID 21062666.
- ^ Looareesuwan S, Viravan C, Vanijanonta S, et al. (1992). "Randomised trial of artesunate and mefloquine alone and in sequence for acute uncomplicated falciparum malaria". Lancet 339 (8797): 821–4. doi:10.1016/0140-6736(92)90276-9. PMID 1347854.
- ^ Nosten F, van Vugt M, Price R, et al. (2000). "Effects of artesunate-mefloquine combination on incidence of Plasmodium falciparum malaria and mefloquine resistance in western Thailand: a prospective study". Lancet 356 (9226): 297–302. doi:10.1016/S0140-6736(00)02505-8. PMID 11071185.
- ^ Adjuik M, Agnamey P, Babiker A, et al. (2002). "Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: a randomised, multicentre trial". Lancet 359 (9315): 1365–72. doi:10.1016/S0140-6736(02)08348-4. PMID 11978332.
- ^ Meremikwu M, Alaribe A, Ejemot R, et al. (2006). "Artemether-lumefantrine versus artesunate plus amodiaquine for treating uncomplicated childhood malaria in Nigeria: randomized controlled trial". Malar J 5: 43. doi:10.1186/1475-2875-5-43. PMC 1475595. PMID 16704735.
- ^ WHO (2007). Assessment of the safety of artemisinin compounds in pregnancy. World Health Organization, Geneva.
- ^ White NJ (2008). "Qinghaosu (Artemisinin): The price of success". Science 320 (5874): 330–334. doi:10.1126/science.1155165. PMID 18420924.
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Antiparasitics – antiprotozoal agents – Chromalveolate antiparasitics (P01)
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|
Alveo-
late |
Apicom-
plexa |
Conoidasida/
(Coccidiostats) |
| Cryptosporidiosis |
|
|
| Isosporiasis |
- trimethoprim/sulfamethoxazole#
|
|
| Toxoplasmosis |
- pyrimethamine
- sulfadiazine
|
|
|
| Aconoidasida |
| Malaria |
Individual
agents |
Hemozoin
inhibitors |
| aminoquinolines |
- (4-): amodiaquine#
- chloroquine#
- (8-): primaquine#
- pamaquine
|
|
| 4-methanolquinolines |
- mefloquine#
- quinine#
- quinidine
|
|
| Other |
|
|
|
| Antifolates |
DHFR inhibitors
(antifols) |
- proguanil#
- chlorproguanil
|
|
| Sulfonamides |
- sulfadoxine
- sulfamethoxypyrazine
|
|
| Coformulation |
- sulfadoxine/pyrimethamine (SP)#
|
|
|
Sesquiterpene
lactones |
- artemether#
- artesunate#
- dihydroartemisinin
- artemotil
- artemisinin
|
|
| Other |
- atovaquone (with proguanil as Malarone)
- tetracycline
- doxycycline#
- clindamycin
- pyronaridine
- piperaquine
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|
|
Combi-
nations |
| Fixed-dose (coformulated) ACTs |
- artemether/lumefantrine#
- artesunate/amodiaquine (ASAQ)
- artesunate/mefloquine (ASMQ)
- dihydroartemisinin/piperaquine
- artesunate/pyronaridine
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Other combinations
(not co-formulated) |
- artesunate/SP
- artesunate/mefloquine
- quinine/tetracycline
- quinine/doxycycline
- quinine/clindamycin
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|
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| Babesiosis |
|
|
|
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Cilio-
phora |
- Balantidiasis: Tetracycline
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|
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Hetero-
kont |
- Blastocystosis: Metronidazole
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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UpToDate Contents
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English Journal
- Artesunate induces apoptosis via a Bak-mediated caspase-independent intrinsic pathway in human lung adenocarcinoma cells.
- Zhou C, Pan W, Wang XP, Chen TS.SourceMOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China.
- Journal of cellular physiology.J Cell Physiol.2012 Dec;227(12):3778-86. doi: 10.1002/jcp.24086.
- This report is designed to explore the exact molecular mechanism by which artesunate (ART), a semisynthetic derivative of the herbal antimalaria drug artemisinin, induces apoptosis in human lung adenocarcinoma (ASTC-a-1 and A549) cell lines. ART treatment induced ROS-mediated apoptosis in a concentr
- PMID 22378505
- Pharmacokinetics and Pharmacodynamics of Oral Artesunate Monotherapy in Patients with Uncomplicated Plasmodium falciparum Malaria in Western Cambodia.
- Saunders D, Khemawoot P, Vanachayangkul P, Siripokasupkul R, Bethell D, Tyner S, Se Y, Rutvisuttinunt W, Sriwichai S, Chanthap L, Lin J, Timmermans A, Socheat D, Ringwald P, Noedl H, Smith B, Fukuda M, Teja-Isavadharm P.SourceDepartment of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
- Antimicrobial agents and chemotherapy.Antimicrob Agents Chemother.2012 Nov;56(11):5484-93. doi: 10.1128/AAC.00044-12. Epub 2012 Aug 6.
- Artemisinin-resistant malaria along the Thailand-Cambodian border is an important public health concern, yet mechanisms of drug action and their contributions to the development of resistance are poorly understood. The pharmacokinetics and pharmacodynamics of oral artesunate monotherapy were explore
- PMID 22869581
Japanese Journal
- Artemisinin-based combination therapies and their introduction in Japan
- KANO Shigeyuki
- Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 16(6), 375-382, 2010-12-01
- NAID 10027655912
- Artesunate inhibiting angiogenesis induced by human myeloma RPMI8226 cells
- CHEN Hao,SHI Liang,YANG Xiaoyang,LI Shihui,GUO Xiaoling,PAN Ling
- International journal of hematology 92(4), 587-597, 2010-11-15
- NAID 10027673888
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- Uses [edit source | edit] Artesunate is used primarily as treatment for malaria; it has also been shown to be >90% efficacious at reducing egg production in Schistosoma haematobium infection. [1] According to WHO intravenous AS ...
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