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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Malaria Journal 1/2012

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

Zeitschrift:
Malaria Journal > Ausgabe 1/2012
Autoren:
Aurélie Pascual, 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
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2875-11-45) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests. The conclusions presented in this article were not financially influenced.

Authors' contributions

AP, CR and BP conceived, designed, carried out in vitro testing of drug susceptibility, analysed the data and drafted the manuscript. PP, FBV, FS, DM, SP, PD, DB, DM, BF, GM and NB carried out diagnostic, monitoring patients, collected clinical and epidemiological data. CO and ED conceived, designed and drafted the manuscript. All authors read and approved the final manuscript.

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.
Zusatzmaterial
Authors’ original file for figure 1
12936_2011_2016_MOESM1_ESM.pdf
Literatur
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