Artemisinin

Artemisinin and its derivatives are sesquiterpene lactones used primarily in the treatment of malaria, especially the most lethal form caused by Plasmodium falciparum; also, it is currently being investigated as a possible antineoplastic due to its antiangiogenic and selectively oxidizing effect. The classic form is a plant product from the herb qinghaosu used in traditional Chinese medicine.

To prevent the development of artemisinin resistance in P. falciparum, the WHO discourages artemisinin monotherapy, instead recommending combining artemisinin with other antimalarial drugs, which has been termed 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.

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. 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

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.

The problem is aggravated by the extensive worldwide practice of self-medication for malaria, coupled with widespread distribution of counterfeit drugs.

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."

Antineoplastic

Artemisinin is currently being investigated as a possible cancer treatment. Cancer cells tend to hoard iron; iron in turn can catalyze the decomposition of artemisinin's peroxide moiety, releasing reactive oxygen species which can ultimately result in cancer cell death. Apart from this, artemisinin has been shown to inhibit angiogenesis in-vitro in certain cell cultures.