Chemical Properties
To class white crystalline powder
Definition
ChEBI: An aminoquinoline that is 1,3-di(piperazin-1-yl)propane in which the nitrogen at position 4 of each of the piperazine moieties is replaced by a 7-chloroquinolin-4-yl group.
Biological Activity
piperaquine, an antimalarial drug, is first synthesised in the 1960s and extensively used as prophylaxis and treatment during the next 20 years.
in vitro
in 280 p. falciparum isolates, the ic50 for piperaquine ranged from 9.8 nm to 217.3 nm and a significant but low correlation was observed between the ic50 values for piperaquine and chloroquine. however, the coefficient of determination indicated that only 2.1% of the variation in the response to piperaquine was explained by the variation in the response to chloroquine. moreover, the mean value for piperaquine was 74.0 nm in the pfcrt k76 wild-type group and 87.7 nm in the 76t mutant group and such difference was not significant [1].
in vivo
male sd rats were orally administered piperaquine or as a short-term i.v. infusion. results showed that piperaquine disposition was best described by a 3-compartment model with a rapid initial distribution phase after i.v. administration. the pk of piperaquine was characterized by a low clearance, a large volume of distribution and a long terminal half-life [2].
IC 50
9.8 to 217.3 nm for p. falciparum isolates
References
[1] pascual a et al. in vitro piperaquine susceptibility is not associated with the plasmodium falciparum chloroquine resistance transporter gene. malar j. 2013 nov 25;12:431.
[2] tarning j, lindegardh n, sandberg s, day nj, white nj, ashton m. pharmacokinetics and metabolism of the antimalarial piperaquine after intravenous and oral single doses to the rat. j pharm sci. 2008 aug;97(8):3400-10.
[3] denis mb, davis tm, hewitt s, incardona s, nimol k, fandeur t, poravuth y, lim c, socheat d. efficacy and safety of dihydroartemisinin-piperaquine (artekin) in cambodian children and adults with uncomplicated falciparum malaria. clin infect dis. 2002 dec 15;35(12):1469-76.
