The metabolism of piperaquine to its antiplasmodial metabolites and their pharmacokinetic profiles in healthy volunteers.

The metabolism of piperaquine to its antiplasmodial metabolites and their pharmacokinetic profiles in healthy volunteers. Antimicrob Agents Chemother. 2018 May 21;: Authors: Liu H, Zhou H, Cai T, Yang A, Zang M, Xing J Abstract As a partner antimalarial for artemisinin drug-based combination therapy (ACT), piperaquine (PQ) can be metabolized into two major metabolites, including piperaquine N-oxide (M1) and N,N-dioxide (M2). To better understand the antimalarial potency of PQ, the antimalarial activity of PQ metabolites (M1 and M2) was studied in vitro (Plasmodium strains Pf3D7 and PfDd2) and in vivo (murine Plasmodium yoelii) in this study. The recrudescence and survival time of infected mice were also recorded after drug treatment. The pharmacokinetic profiles of PQ and its two metabolites (M1 and M2) were investigated in healthy subjects after oral doses of two widely used ACT regimens, i.e., Duo-Cotecxin (dihydroartemisinin plus piperaquine phosphate) and Artequick (artemisinin plus piperaquine). Remarkable antiplasmodial activity was found for PQ (IC50 4.5 nM against Pf3D7 and IC50 6.9 nM against PfDd2 strain; ED90 of 1.3 mg/kg), M1 (IC50 25.5 nM against Pf3D7 and IC50 38.7 nM against PfDd2 strain; ED90 of 1.3 mg/kg) and M2 (IC50 31.2 nM against Pf3D7 and IC50 33.8 nM against PfDd2 strain; ED90 of 2.9 mg/kg). Compared with PQ, M1 showed comparable efficacy, in terms of recrudescence and survival time, and M2 had relatively weake...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research