<it>Ex vivo </it>activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of <it>Plasmodium falciparum</it>
<p>Abstract</p> <p>Background</p> <p>The aim of the present work was to assess i) <it>ex vivo </it>activity of pyronaridine (PND) and piperaquine (PPQ), as new components of artemisinin-based combination therapy (ACT), to define susceptibility baseline, ii)...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-02-01
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| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | http://www.malariajournal.com/content/11/1/45 |
| _version_ | 1818808195578068992 |
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| author | Pascual Aurélie Parola Philippe Benoit-Vical Françoise Simon Fabrice Malvy Denis Picot Stéphane Delaunay Pascal Basset Didier Maubon Danièle Faugère Bernard Ménard Guillaume Bourgeois Nathalie Oeuvray Claude Didillon Eric Rogier Christophe Pradines Bruno |
| author_facet | Pascual Aurélie Parola Philippe Benoit-Vical Françoise Simon Fabrice Malvy Denis Picot Stéphane Delaunay Pascal Basset Didier Maubon Danièle Faugère Bernard Ménard Guillaume Bourgeois Nathalie Oeuvray Claude Didillon Eric Rogier Christophe Pradines Bruno |
| author_sort | Pascual Aurélie |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The aim of the present work was to assess i) <it>ex vivo </it>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 <it>Plasmodium falciparum </it>isolates from African countries, India and Thailand, and iii) <it>in vitro </it>cross-resistance with other quinoline drugs, chloroquine (CQ) or quinine (QN).</p> <p>Methods</p> <p>The susceptibility of the 181 <it>P. falciparum </it>isolates to the nine anti-malarial drugs was assessed using the standard 42-hours <sup>3</sup>H-hypoxanthine uptake inhibition method.</p> <p>Results</p> <p>The IC<sub>50 </sub>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 (<it>rho </it>= 0.46) and between PPQ and MDAQ (<it>rho </it>= 0.30). No significant correlation was shown between PPQ IC<sub>50 </sub>and responses to other anti-malarial drugs. A significant positive correlation was shown between responses to PND and MDAQ (<it>rho </it>= 0.37), PND and LMF (<it>rho </it>= 0.28), PND and QN (<it>rho </it>= 0.24), PND and AS (<it>rho </it>= 0.19), PND and DHA (<it>rho </it>= 0.18) and PND and CQ (<it>rho </it>= 0.16). All these coefficients of correlation are too low to suggest cross-resistance between PPQ or PND and the other drugs.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-12-18T19:37:42Z |
| format | Article |
| id | doaj.art-9ec13234059144b18c4e63182e29403b |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-18T19:37:42Z |
| publishDate | 2012-02-01 |
| publisher | BMC |
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| series | Malaria Journal |
| spelling | doaj.art-9ec13234059144b18c4e63182e29403b2022-12-21T20:55:32ZengBMCMalaria Journal1475-28752012-02-011114510.1186/1475-2875-11-45<it>Ex vivo </it>activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of <it>Plasmodium falciparum</it>Pascual AurélieParola PhilippeBenoit-Vical FrançoiseSimon FabriceMalvy DenisPicot StéphaneDelaunay PascalBasset DidierMaubon DanièleFaugère BernardMénard GuillaumeBourgeois NathalieOeuvray ClaudeDidillon EricRogier ChristophePradines Bruno<p>Abstract</p> <p>Background</p> <p>The aim of the present work was to assess i) <it>ex vivo </it>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 <it>Plasmodium falciparum </it>isolates from African countries, India and Thailand, and iii) <it>in vitro </it>cross-resistance with other quinoline drugs, chloroquine (CQ) or quinine (QN).</p> <p>Methods</p> <p>The susceptibility of the 181 <it>P. falciparum </it>isolates to the nine anti-malarial drugs was assessed using the standard 42-hours <sup>3</sup>H-hypoxanthine uptake inhibition method.</p> <p>Results</p> <p>The IC<sub>50 </sub>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 (<it>rho </it>= 0.46) and between PPQ and MDAQ (<it>rho </it>= 0.30). No significant correlation was shown between PPQ IC<sub>50 </sub>and responses to other anti-malarial drugs. A significant positive correlation was shown between responses to PND and MDAQ (<it>rho </it>= 0.37), PND and LMF (<it>rho </it>= 0.28), PND and QN (<it>rho </it>= 0.24), PND and AS (<it>rho </it>= 0.19), PND and DHA (<it>rho </it>= 0.18) and PND and CQ (<it>rho </it>= 0.16). All these coefficients of correlation are too low to suggest cross-resistance between PPQ or PND and the other drugs.</p> <p>Conclusions</p> <p>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.</p>http://www.malariajournal.com/content/11/1/45Malaria<it>Plasmodium falciparum</it>Anti-malarial<it>In vitro</it>ResistancePyronaridinePiperaquine |
| spellingShingle | Pascual Aurélie Parola Philippe Benoit-Vical Françoise Simon Fabrice Malvy Denis Picot Stéphane Delaunay Pascal Basset Didier Maubon Danièle Faugère Bernard Ménard Guillaume Bourgeois Nathalie Oeuvray Claude Didillon Eric Rogier Christophe Pradines Bruno <it>Ex vivo </it>activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of <it>Plasmodium falciparum</it> Malaria Journal Malaria <it>Plasmodium falciparum</it> Anti-malarial <it>In vitro</it> Resistance Pyronaridine Piperaquine |
| title | <it>Ex vivo </it>activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of <it>Plasmodium falciparum</it> |
| title_full | <it>Ex vivo </it>activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of <it>Plasmodium falciparum</it> |
| title_fullStr | <it>Ex vivo </it>activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of <it>Plasmodium falciparum</it> |
| title_full_unstemmed | <it>Ex vivo </it>activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of <it>Plasmodium falciparum</it> |
| title_short | <it>Ex vivo </it>activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of <it>Plasmodium falciparum</it> |
| title_sort | it ex vivo it activity of the act new components pyronaridine and piperaquine in comparison with conventional act drugs against isolates of it plasmodium falciparum it |
| topic | Malaria <it>Plasmodium falciparum</it> Anti-malarial <it>In vitro</it> Resistance Pyronaridine Piperaquine |
| url | http://www.malariajournal.com/content/11/1/45 |
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