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

Malaria Journal

Research

Eric Didillon¹  Guillaume Ménard²  Philippe Parola³  Bernard Faugère⁴  Didier Basset⁵  Françoise Benoit-Vical⁶  Danièle Maubon⁷  Pascal Delaunay⁸  Stéphane Picot⁹  Claude Oeuvray^1,10  Nathalie Bourgeois^1,11  Fabrice Simon^1,12  Denis Malvy^1,13  Christophe Rogier^1,14  Bruno Pradines^1,15  Aurélie Pascual^1,15 

[1] Fulcrum Pharma (Europe) Ltd, Hemel Hempstead, UK;Fédération des Laboratoires, Hôpital d'Instruction des Armées Sainte Anne, Toulon, France;Institut Hospitalo-Universitaire en Maladies Infectieuses et Tropicales, Hôpital Nord, Marseille, France;Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Universitaire La Timone, Marseille, France;Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Universitaire Lapeyronnie, Montpellier, France;Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Universitaire de Rangueil, Toulouse, France;Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Universitaire et Université de Grenoble 1, Grenoble, France;Laboratoire de Parasitologie-Mycologie, Hopital de 1'Archet, Nice, France;Malaria Research Unit, UMR 5246, CNRS Lyon, France;Medicines for Malaria Venture, Geneva, Switzerland;Service de Bactériologie-Virologie-Parasitologie, Centre Hospitalier Universitaire Caremeau, Nimes, France;Service de Pathologie Infectieuse et Tropicale, Hôpital d'Instruction des Armées Laveran, Marseille, Frnace;Travel Clinics and Division of Tropical Medicine and Imported Diseases, Centre Hospitalier Universitaire, Bordeaux, France;Unité de Recherche en Biologie et Epidémiologie Parasitaires Unité de Recherche pour les Maladies Infectieuses et Tropicales Emergentes UMR--6236, Institut de Recherche Biomédicale des Armées, Allée du Médecin-colonel Jamot, BP 60109, 13262, Marseille, Cedex, France;Unité de Recherche en Biologie et Epidémiologie Parasitaires Unité de Recherche pour les Maladies Infectieuses et Tropicales Emergentes UMR--6236, Institut de Recherche Biomédicale des Armées, Allée du Médecin-colonel Jamot, BP 60109, 13262, Marseille, Cedex, France;Centre National de Référence du Paludisme, Marseille, France;

关键词: Malaria;    Plasmodium falciparum;    Anti-malarial;    In vitro;    Resistance;    Pyronaridine;    Piperaquine;   

DOI  :  10.1186/1475-2875-11-45

 received in 2011-10-17, accepted in 2012-02-14,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe 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).MethodsThe 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.ResultsThe 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.ConclusionsIn 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.

【 授权许可】

Unknown   
© Pascual et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.