Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2012 Feb 14:11:45.
doi: 10.1186/1475-2875-11-45.

Ex vivo activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of Plasmodium falciparum

Aurélie Pascual  1 , Philippe Parola, Françoise Benoit-Vical, Fabrice Simon, Denis Malvy, Stéphane Picot, Pascal Delaunay, Didier Basset, Danièle Maubon, Bernard Faugère, Guillaume Ménard, Nathalie Bourgeois, Claude Oeuvray, Eric Didillon, Christophe Rogier, Bruno Pradines
Affiliations
Comparative Study

Ex vivo activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of Plasmodium falciparum

Aurélie Pascual et al. Malar J. .

Abstract

Background: The aim of the present work was to assess i) ex vivo activity of pyronaridine (PND) and piperaquine (PPQ), as new components of artemisinin-based combination therapy (ACT), to define susceptibility baseline, ii) their activities compared to other partner drugs, namely monodesethylamodiaquine (MDAQ), lumefantrine (LMF), mefloquine (MQ), artesunate (AS) and dihydroartemisinin (DHA) against 181 Plasmodium falciparum isolates from African countries, India and Thailand, and iii) in vitro cross-resistance with other quinoline drugs, chloroquine (CQ) or quinine (QN).

Methods: The susceptibility of the 181 P. falciparum isolates to the nine anti-malarial drugs was assessed using the standard 42-hours 3H-hypoxanthine uptake inhibition method.

Results: The IC50 values for PND ranged from 0.55 to 80.0 nM (geometric mean = 19.9 nM) and from 11.8 to 217.3 nM for PPQ (geometric mean = 66.8 nM). A significant positive correlation was shown between responses to PPQ and PND responses (rho = 0.46) and between PPQ and MDAQ (rho = 0.30). No significant correlation was shown between PPQ IC50 and responses to other anti-malarial drugs. A significant positive correlation was shown between responses to PND and MDAQ (rho = 0.37), PND and LMF (rho = 0.28), PND and QN (rho = 0.24), PND and AS (rho = 0.19), PND and DHA (rho = 0.18) and PND and CQ (rho = 0.16). All these coefficients of correlation are too low to suggest cross-resistance between PPQ or PND and the other drugs.

Conclusions: In this study, the excellent anti-malarial activity of PPQ and PND was confirmed. The absence of cross-resistance with quinolines and artemisinin derivatives is consistent with the efficacy of the combinations of PPQ and DHA or PND and AS in areas where parasites are resistant to conventional anti-malarial drugs.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Dot plots of IC50 values in nM for chloroquine (CQ), quinine (QN), pyronaridine (PND), piperaquine (PPQ), mefloquine (MQ), monodesethylamodiaquine (MDAQ), lumefantrine (LMF), dihydroartemisinin (DHA) and artesunate (AS). Each dot represents one isolate.
See this image and copyright information in PMC

References

    1. Le Bras J, Musset L, Clain J. Antimalarial drug resistance. Med Mal Infect. 2006;36:401–405. doi: 10.1016/j.medmal.2006.05.005. - DOI - PubMed
    1. White NJ. Preventing antimalarial drug resistance through combinations. Drug Resist Update. 2001;1:3–9. - PubMed
    1. Eastman RT, Fidock DA. Artemisinin-based combination therapies: a vital tool in efforts to eliminate malaria. Nat Rev Microbiol. 2009;7:864–874. - PMC - PubMed
    1. Von Seidlein L, Milligan P, Pinder M, Bojang K, Anyalebechi C, Gosling R, Coleman R, Ude JI, Sadiq A, Duraisingh M, Warhurst D, Alloueche A, Target G, Mcadam K, Greenwood B, Walraven G, Olliaro P, Doherty T. Efficacy of artesunate plus pyrimethamine-sulphadoxine for uncomplicated malaria in the Gambian children: a double-blind, randomized, controlled trial. Lancet. 2000;355:352–357. doi: 10.1016/S0140-6736(99)10237-X. - DOI - PubMed
    1. Brasseur P, Agnamey P, Gaye O, Vaillant M, Taylor WRJ, Olliaro PL. Efficacy and safety of artesunate plus amodiaquine in routine use for the treatment of uncomplicated malaria in Casamance, southern Senegal. Malar J. 2007;6:150. doi: 10.1186/1475-2875-6-150. - DOI - PMC - PubMed

Publication types