Quinoline, 4,4′-(1,3-propanediyldi-4,1-piperazinediyl)bis[7-chloro-

633.51

535.51

A0HV2Q956Y

DTXSID00193825

2933990090

38.7

5.15

Almost wite powder

1.3±0.1 g/cm3

198-200 °C

721.1±60.0 °C at 760 mmHg

389.9±32.9 °C

1.664

Studies of piperaquine in monkeys and dogs have shown some hepatotoxicity and reversible depression in white blood cells and neutrophils. Additional observations include infiltration of macrophages with intracytoplasmic basophilic granular material consistent with phospholipidosis and degenerative lesions in numerous organs and tissues. These effects were seen at exposure levels similar to clinical dosing in humans. At high doses, piperaquine can interfere with cardiac conduction and produce effects on blood pressure. Mild phototoxicity has been observed with piperaquine in rats exposed to UV light.

Piperaquine's binding to plasma proteins is considered to be virtually complete. It has been measured to be >99% in humans, rats, and dogs.

For the treatment of uncomplicated *Plasmodium falciparum* infection in adults, children, and infants aged 6 months and up weighing over 5 kg. Used in combination with [DB11638].|FDA Label

Piperaquine inhibits the P. Falciparum parasite's haem detoxification pathway.

Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585) (See all compounds classified as Antimalarials.)

Piperaquine is slowly absorbed and exhibits multiple peaks in its plasma concentration curve suggestive of enterohepatic recycling occurring alongside the absorption process. Due to this complication there is no discreet value for bioavailability but piperaquine is highly absorbed into systemic circulation. When taken with food, Cmax increases by 217% and mean exposure increases by 177%. Tmax is not affected by food and remains around 5 h. Piperaquine has been observed to accumulate more in females to a degree of 30-50% more than males. It also collects in red blood cells similar to [DB11638].|Piperaquine is mainly excreted in the feces with a negligible amount in the urine.|Piperaquine is thought to distribute into a central compartment with an apparent volume of 26.7 L/kg, and two peripheral compartments with apparent volumes of 76.8 L/kg and 617 L/kg. These combine for a total volume of distribution of 720.5 L/kg.|The mean apparent total clearance has been observed to be 1.12 L/h/kg in adult malaria patients.

Piperaquine undergoes N-dealkylation, separating its aliphatic bridge from one of the nitrogen-containing rings. The resulting aldehyde is then oxidized to a carboxylic acid to form metabolite 1 (M1). The same nitrogen-containing rings can also undergo hydroxylation at one of two sites to form M3 or M4. M2 is formed via N-oxidation of one of the nitrogens in the quinoline groups at either side of the molecule. M5 results when both of these nitrogens are oxidized. M1 and M2 are the major metabolism products. Each of these metabolites were observed in the urine.

The terminal elimination half-life was observed to be 576h or 24 days. This is thought to be due to the extensive distribution of piperaquine.

The mechanism of piperaquine inhibition of the haem detoxification pathway is unknown but is expected to be similar to that of [DB00608].

1,3-bis(1-(7-chloro-4'-quinolyl)-4'-piperazinyl)propane