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| Formula | C29H32Cl2N6 |
| Molar mass | 535.52 g·mol−1 |
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| Melting point | 199 to 204 °C (390 to 399 °F) (dec.V |
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Piperaquine is an antiparasitic drug used in combination withdihydroartemisinin to treatmalaria. Piperaquine was developed under the Chinese National Malaria Elimination Programme in the 1960s and was adopted throughout China as a replacement for the structurally similar antimalarial drug chloroquine. Due to widespread parasite resistance to piperaquine, the drug fell out of use as amonotherapy, and is instead used as a partner drug forartemisinin combination therapy. Piperaquine kills parasites by disrupting the detoxification of hostheme.
Piperaquine is used in combination withdihydroartemisinin for the treatment of malaria.[1] This combination is one of severalartemisinin combination therapies recommended by the World Health Organization for treatment ofuncomplicated malaria.[1] This combination is also recommended by the World Health Organization for treatment ofsevere malaria after administration ofartesunate.[1]
Piperaquine is also registered for use in some countries in combination witharterolane.[1] However, this combination is not recommended by the World Health Organization due to insufficient data.[1]
Likechloroquine, piperaquine can prolong theQT interval. Although large randomized clinical trials have not revealed evidence ofcardiotoxicity, the World Health Organization recommends not using piperaquine in patients with congenital QT prolongation or who are on otherdrugs that prolong the QT interval.[1]
Like chloroquine, piperaquine is thought to function by accumulating in the parasitedigestive vacuole and interfering with the detoxification ofheme intohemozoin.[2]
Parasites that survive piperaquine treatment have been increasingly reported since 2010, particularly in Southeast Asia. The epicenter of piperaquine resistance appears to be westernCambodia where in 2014 over 40% of dihydroartemisinin-piperaquine treatments failed to eliminate parasites from the patient's blood.[3] Characterizing piperaquine-resistant parasites has been technically challenging, as parasites that survive piperaquine treatment in patients appear to remain sensitive to piperaquinein vitro; i.e. piperaquine appears to have the sameIC50 in sensitive parasites and resistant parasites.[3]
The mechanism by which parasites become resistant to piperaquine remains unclear. Amplification of the parasite proteasesplasmepsin 2 andplasmepsin 3, both involved in degrading host hemoglobin, is associated with resistance to piperaquine.[4] Similarly, mutations in a gene related to chloroquine resistance,PfCRT, have been associated with piperaquine resistance; however, parasites that are resistant to chloroquine remain sensitive to piperaquine.[4][3] In contrast, amplification of the gene for the parasite transporterPfMDR1, a mechanism of parasite resistance tomefloquine, is inversely correlated with piperaquine resistance.[3]
Piperaquine is alipophilic drug and therefore is rapidly absorbed anddistributed across much of the body.[2] The drug reaches its maximal concentrations approximately 2 hours after administration.[2]
Piperaquine is available as a base, and as a water-soluble tetraphosphate salt.[5]
Piperaquine was discovered in the 1960s by two separate groups working independently of one another: theShanghai Pharmaceutical Industry Research Institute in China and theRhone Poulenc in France.[5] In the 1970s and 1980s piperaquine became the primary antimalarial drug of the Chinese National Malaria Control Programme due to increased parasite resistance to chloroquine.[2] By the late 1980s, the use of piperaquine as an antimalarial monotherapy diminished as increasing parasite resistance to piperaquine was observed.[5] Beginning in the 1990s, piperaquine was tested and adopted as a partner drug forartemisinin combination therapy.[5]
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