Artemisinin: Difference between revisions
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'''Artemisinin''' and its derivatives are now the most important drugs in the treatment of [[malaria]], especially the most lethal form caused by ''[[Plasmodium falciparum]]''. The classic form is a [[phytotherapy|plant product]] used in [[traditional Chinese medicine]]. | '''Artemisinin''' and its derivatives are now the most important drugs in the treatment of [[malaria]], especially the most lethal form caused by ''[[Plasmodium falciparum]]''. The classic form is a [[phytotherapy|plant product]] from the herb [[qinghaosu]] used in [[traditional Chinese medicine]]. | ||
To reduce the development of [[#resistance|resistant ''Plasmodia'']], the standard of care is to use it in jointly with other antimalarial drugs: '''artemisinin combination therapy (ACT)'''. | To reduce the development of [[#resistance|resistant ''Plasmodia'']], the standard of care is to use it in jointly with other antimalarial drugs: '''artemisinin combination therapy (ACT)'''. | ||
==Class drug and derivatives== | ==Class drug and derivatives== | ||
Artemisin itself has | Artemisin itself has relatively low bioavailability and has been banned in some countries, to avoid resistance formation due to underdosage. | ||
Artesunate is a derivative that produces higher blood levels when given intravenously. In 2007, the U.S. [[Centers for Disease Control]] (CDC) received an exception from the [[Food and Drug Administration]] to Artesunate in the United States, specifically for treatment of malarial clinical emergencies; CDC will dispense it to requesting organizations that meet treatment criteria. | Artesunate is a derivative that produces higher blood levels when given intravenously. In 2007, the U.S. [[Centers for Disease Control]] (CDC) received an exception from the [[Food and Drug Administration]] to Artesunate in the United States, specifically for treatment of malarial clinical emergencies; CDC will dispense it to requesting organizations that meet treatment criteria. | ||
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}}</ref> | }}</ref> | ||
===Counterfeiting=== | ===Counterfeiting=== | ||
<ref>{{citation | A collaborative effort based around the [[World Health Organization]] and [[INTERPOL]] began in May 2005 when it became clear the counterfeit artesunate situation was worsening in the Greater Mekong Sub-Region of South East Asia (comprising [[Cambodia]], [[Laos|Lao People's Democratic Republic]], [[Myanmar]], [[Thailand]], [[Vietnam]], and [[Yunnan Province]] of the [[People's Republic of China]]). "Chemical analysis revealed that all tablets thought to be fake contained no or very small quantities of artesunate. Other ingredients found in the artesunate counterfeit tablets included paracetamol, antibiotics, older antimalarial drugs, and a range of minerals, and there were a variety of gases surrounding the tablets inside the packaging. Biological analyses of pollen grains inside the packaging suggested that the packages originated in the parts of South East Asia along the Chinese border...two regional clusters where the counterfeit tablets appeared to be coming from, thus flagging a potential manufacturing site or distribution network. The presence of wrong active pharmaceutical ingredients (such as the older antimalarial drugs) suggested the counterfeiters had access to a variety of active pharmaceutical ingredients. The presence of [[safrole]], a precursor to the illicit drug [[(3, 4-Methylenedioxymethamphetamine|Ecstasy or MDMA]], suggested the counterfeits may be coming from factories that manufacture Ecstasy. And the identification of minerals indigenous to certain regions also helped identify the counterfeits' origin. The researchers concluded that at least some of the counterfeit artesunate was coming from southern China. The Secretary General of INTERPOL presented the findings to the Chinese government, which then carried out a criminal investigation and arrested individuals alleged to have produced and distributed the counterfeit artesunate."<ref>{{citation | ||
| title = A Collaborative Epidemiological Investigation into the Criminal Fake Artesunate Trade in South East Asia | | title = A Collaborative Epidemiological Investigation into the Criminal Fake Artesunate Trade in South East Asia | ||
| author = Newton PN, Fernández FM, Plançon A, Mildenhall DC, Green MD, et al. | year =2008 | | author = Newton PN, Fernández FM, Plançon A, Mildenhall DC, Green MD, et al. | year =2008 | ||
Revision as of 14:44, 30 December 2009
Artemisinin and its derivatives are now the most important drugs in the treatment of malaria, especially the most lethal form caused by Plasmodium falciparum. The classic form is a plant product from the herb qinghaosu used in traditional Chinese medicine.
To reduce the development of resistant Plasmodia, the standard of care is to use it in jointly with other antimalarial drugs: artemisinin combination therapy (ACT).
Class drug and derivatives
Artemisin itself has relatively low bioavailability and has been banned in some countries, to avoid resistance formation due to underdosage.
Artesunate is a derivative that produces higher blood levels when given intravenously. In 2007, the U.S. Centers for Disease Control (CDC) received an exception from the Food and Drug Administration to Artesunate in the United States, specifically for treatment of malarial clinical emergencies; CDC will dispense it to requesting organizations that meet treatment criteria. [1]
Resistance
The main drivers of the developing resistance are under-dosing and counterfeit drugs. One study found that 88 percent of the drugs purchased at local markets contained no or substandard amounts of artemisinin. Many people cannot afford to buy a full treatment course and may therefore be under-dosed even if the drugs contained correct amounts of artemisinin.[2] An editorial in Expert Opinion of Anti-Infective Therapy suggested that the only rational way of stopping the spread of artemisinin resistance was to deliver the drug free of charge [3]
Several drug combinations, however, such as artesunate, when used with older antimalarial drugs against which resistance already exists, may produce treatment failures, which already may have happened in the historically drug-resistant border between Cambodia and Thailand. [4]
The problem is aggravated by the extensive worldwide practice of self-medication for malaria, coupled with widespread distribution of counterfeit drugs.[5]
Counterfeiting
A collaborative effort based around the World Health Organization and INTERPOL began in May 2005 when it became clear the counterfeit artesunate situation was worsening in the Greater Mekong Sub-Region of South East Asia (comprising Cambodia, Lao People's Democratic Republic, Myanmar, Thailand, Vietnam, and Yunnan Province of the People's Republic of China). "Chemical analysis revealed that all tablets thought to be fake contained no or very small quantities of artesunate. Other ingredients found in the artesunate counterfeit tablets included paracetamol, antibiotics, older antimalarial drugs, and a range of minerals, and there were a variety of gases surrounding the tablets inside the packaging. Biological analyses of pollen grains inside the packaging suggested that the packages originated in the parts of South East Asia along the Chinese border...two regional clusters where the counterfeit tablets appeared to be coming from, thus flagging a potential manufacturing site or distribution network. The presence of wrong active pharmaceutical ingredients (such as the older antimalarial drugs) suggested the counterfeiters had access to a variety of active pharmaceutical ingredients. The presence of safrole, a precursor to the illicit drug Ecstasy or MDMA, suggested the counterfeits may be coming from factories that manufacture Ecstasy. And the identification of minerals indigenous to certain regions also helped identify the counterfeits' origin. The researchers concluded that at least some of the counterfeit artesunate was coming from southern China. The Secretary General of INTERPOL presented the findings to the Chinese government, which then carried out a criminal investigation and arrested individuals alleged to have produced and distributed the counterfeit artesunate."[6]
References
- ↑ Jorge Rivas (2 August 2007), "CDC to Distribute Novel Drug for the Treatment of Malaria Emergencies", Associated Content
- ↑ Sengaloundeth et al. (2009), "A stratified random survey of the proportion of poor quality oral artesunate sold at medicine outlets in the Lao PDR - implications for therapeutic failure and drug resistance", Malar J. 8: 172
- ↑ Schlagenhauf P and Petersen E (2009), "Antimalaria drug resistance: the mono-combi-counterfeit triangle", Expert Rev Anti Infect Ther 7: 1039-42
- ↑ Wongsrichanalai C, Meshnick SR (2008 May), "Declining artesunate-mefloquine efficacy against falciparum malaria on the Cambodia–Thailand border", Emerg Infect Dis [serial on the Internet]
- ↑ Malaria, Artemisin Resistance, Southeast Asia, ProMED, International Society for Infectious Diseases mailing list, 29 Dec 2009
- ↑ Newton PN, Fernández FM, Plançon A, Mildenhall DC, Green MD, et al. (2008), "A Collaborative Epidemiological Investigation into the Criminal Fake Artesunate Trade in South East Asia", PLoS Med 5(2): e32, DOI:10.1371/journal.pmed.0050032