Piperaquine

Piperaquine

Chemical structure of Piperaquine

Piperaquine is an antimalarial drug that is used in combination with other medications to treat malaria. It is a bisquinoline compound that has been used in the treatment of malaria since the 1960s. Piperaquine is often combined with dihydroartemisinin to form a combination therapy known as dihydroartemisinin-piperaquine (DHA-PPQ), which is effective against Plasmodium falciparum and Plasmodium vivax.

History

Piperaquine was first synthesized in the 1960s and was widely used in China and Indochina as a monotherapy for malaria. However, due to the development of resistance, its use declined. In the 1990s, piperaquine was rediscovered as a partner drug in artemisinin-based combination therapies (ACTs), which are now the standard treatment for malaria.

Mechanism of Action

Piperaquine works by interfering with the hemoglobin digestion process of the malaria parasite. It inhibits the formation of hemozoin, a crystalline substance that the parasite uses to detoxify free heme, which is toxic to the parasite. This leads to the accumulation of toxic heme and ultimately the death of the parasite.

Pharmacokinetics

Piperaquine is administered orally and has a long half-life, which allows for once-daily dosing. It is highly lipophilic and is distributed widely in the body. The drug is metabolized in the liver and excreted primarily in the feces.

Clinical Use

Piperaquine is used in combination with dihydroartemisinin as a first-line treatment for uncomplicated malaria. The combination is effective against both chloroquine-resistant and multidrug-resistant strains of Plasmodium falciparum. It is also used in the treatment of Plasmodium vivax malaria.

Side Effects

Common side effects of piperaquine include headache, dizziness, and gastrointestinal disturbances such as nausea and vomiting. In rare cases, it can cause QT interval prolongation, which can lead to cardiac arrhythmias.

Resistance

Resistance to piperaquine has been reported, particularly in Southeast Asia. The mechanism of resistance is not fully understood but is thought to involve mutations in the parasite's genome that affect drug uptake and metabolism.

Related Pages

• Malaria
• Dihydroartemisinin
• Plasmodium falciparum
• Plasmodium vivax
• Chloroquine