Therapeutics of Artemisia annua
Tariq Aftab, M. Naeem, M. Masroor, A. Khan in Artemisia annua, 2017
Artemether is formed by the conversion of DHA into methyl ester in a two-step procedure, and is stable at room temperature (Valecha and Tripathi,1997). It was first synthesized by Li Yin in 1978 (Jansen and Zhimin,1997). Mohmad et al. (1999) determined artemether in plasma through gas chromatography–mass spectrometry. It is available as an injection of 80 mg, which was soluble in oil for intramuscular use. The dose of this compound was 3.2 mg/kg intramuscularly as a loading dose followed by 1.6 mg/kg orally, daily for a maximum of seven days (Kakkilaya, 2002). β-Artemether is a novel antimalarial drug, which is more active than the parent compound, artemisinin (WHO, 1985). β-Artemether is produced in Belgium under the trade name is Artenam®. It is also marketed under the trade name Paluther® and is manufactured in India by Ipca laboratories under the trade name Larither®.
Globalisation of Traditional Medicine under the Modern Medicine Portfolio
Dilip Ghosh, Pulok K. Mukherjee in Natural Medicines, 2019
Archaeological evidence reveals that drug taking is an extremely old human phenomenon. By necessity, the drugs used in ancient civilisation were extracts of plants or animal products, with a few inorganic salts. In India, the Ayurvedic system of medicine developed an extensive use of medicines from plants dating from at least 1000 BCE. The earliest Chinese records give descriptions of diseases, but not medicines; illnesses were thought to be godly punishments and they were treated by prayers and offerings. The earliest recorded Chinese prescriptions after about 500 BCE show the beginning of the use of natural products as drugs. The first classic texts in Chinese medicine appeared in 25–220 CE, and some of their formulae remains in use (Mukherjee et al. 2010b). Similarly, the Egyptian Ebers papyrus (around 1550 BCE) contains descriptions of several active ingredients (notably purgatives) that are still used today. Western medicine continues to show the influence of ancient practices. Current examples are the use of cardiac glycosides from the purple foxglove Digitalis purpurea and related plants, opiates from the opium poppy Papaver somniferum, reserpine from Rauwolfia species and quinine from Cinchona species. More recently, there has been interest in other products from traditional systems of medicine; artemisinin is an active antimalarial compounds isolated from Artemisia annua, a constituent of the Chinese antimalarial preparation qinghaosu, and forskolin was isolated from Coleus forskohlii, a species used in Ayurvedic preparations for cardiac disorders. A new standardised preparation, artemether, has recently been introduced for treatment of drug-resistant malaria, and new analogues of forskolin are being tested for a variety of uses (Mukherjee et al. 2015b).
Mechanisms of action
Fazal-I-Akbar Danish, Ahmed Ehsan Rabbani in Pharmacology in 7 Days for Medical Students, 2018
Artemether is a potent antimalarial drug used for the treatment of multi-drug resistant plasmodium falciparum infection and cerebral malaria. It is derived from Qinghaosu plant and has been in use in Chinese medicine since ancient times. Just like chloroquine, this drug preferentially concentrates in the food vacuoles of plasmodium, where it is metabolised to form toxic free radicals. Additionally, it appears that this drug covalently binds to specific malarial proteins, damaging and thus rendering them non-functional.
The enhanced treatment efficacy of invasive brain glioma by dual-targeted artemether plus paclitaxel micelles
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2020
Xiuying Li, Luanxia Shi, Yandong Li, Qinqing Li, Xiujun Duan, Yingli Wang, Qingshan Li
Paclitaxel is a high-efficiency anticancer agent, which is extracted from Taxus genus. Paclitaxel has significant therapeutic effects on the various solid tumours including glioma [11,12]. However, it shows unsatisfactory efficacy against invasive gliomas for the poor distribution in tumour site prevented by the BBB [13]. Artemether is a fat-soluble derivative of artemisinin, which has the advantages of rapid absorption and high permeability, and it is often used for anti-cancer research due to the potent cytotoxic activities against tumour cells [14]. Studies have shown that artemether can significantly enhance the VM damage effects [9], and the mechanism is related to the potential down-regulation of matrix metalloproteinase-2 (MMP-2) and hypoxia-inducible factor-α (HIF-α). However, paclitaxel and artemether are inferior in water solubility, and it is tough to maintain an effective concentration in tumour sites.
The preclinical discovery and development of rectal artesunate for the treatment of malaria in young children: a review of the evidence
Published in Expert Opinion on Drug Discovery, 2021
Laís Pessanha de Carvalho, Andrea Kreidenweiss, Jana Held
Artemisinin and related compounds (artesunate, dihydroartemisinin, artemether) are the mainstay malaria drugs. WHO recommends artemisinin-based combination therapies (ACT) as first line therapy for uncomplicated malaria. For severe malaria, parenteral artesunate or, if unavailable, intramuscular artemether should be administered and only if these two drugs are not available intravenous quinine is recommended. All parenteral drug administrations should be followed by three-day oral ACT (as soon as oral medication is tolerated) [7,11]. Parenteral artesunate is superior compared to quinine in reducing mortality, this was confirmed in adults in Asia (mortality reduction of 38.6%) [12] and in children in Africa (22.5%) [13]. Artemisinins are safe, fast-acting, and active against all stages of the asexual life cycle of P. falciparum, rapidly reducing parasite load and are therefore especially suited to be given in severe malaria to prevent further progression of the disease [14]. However, because of their short half-life (30–184 min for dihydroartemisinin, the active metabolite) they are partnered to an antimalarial drug with a longer half-life to obtain complete cure [15]. Resistance to artemisinins exist and are present in many regions of Southeast Asia displayed in form of a delayed clearance phenotype that is associated with a mutation in the kelch13 gene of P. falciparum [16]. There is the fear of spread to Africa, but so far artemisinin resistances/the delayed clearance phenotype is not largely present on the continent [16].
Optimization of artemether-loaded NLC for intranasal delivery using central composite design
Published in Drug Delivery, 2015
Kunal Jain, Sumeet Sood, Kuppusamy Gowthamarajan
Artemether (ARM) is oil soluble methyl ether of artemisinin effective against both chloroquine-resistant and chloroquine-sensitive strains of P. falciparum, as well as against Plasmodium vivax. It is also used in the management of CM (Medana & Turner, 2006). It contains sesquiterpene lactone rings with an endoperoxide bridge that is cleaved by an iron-dependent mechanism. It is a potent inhibitor of cysteine protease by virtue of its inhibition of hemozoin formation as well as hemoglobin degradation (Klayman, 1985). It suffers from poor aqueous solubility and short half life usually between 3 and 5 h. Furthermore, oily intramuscular (i.m) injection of ARM for the treatment of CM is associated with pain on injection, erratic absorbtion and thus poor patient compliance. In addition, i.m. administration is not suited to deliver the drug to treat CM or when quick eradication of the malarial parasite is required (Aditya et al., 2010). Treatment of CM requires hospital admission, since it requires parenteral administration. This is a major limitation as hospitals are not accessible in all the endemic areas (Touitou et al., 2006). Hence to overcome these inherent drawbacks associated with the parenteral delivery of ARM, efforts are being undertaken to investigate alternative modes of antimalarial drug delivery to the brain. The conventional drug delivery system that releases the drug into systemic circulation fails to deliver drugs effectively to brain and is therefore not very useful in treating CM. Therefore, there is need for a patient compliant method to deliver ARM to the brain in a better and effective way.
Related Knowledge Centers
- Arrhythmia
- Artesunate
- Intramuscular Injection
- Malaria
- Plasmodium Falciparum
- Quinine
- Pregnancy
- Artemisinin
- Lumefantrine
- Artemether/Lumefantrine