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In vitro activity of pyronaridine against multidrug-resistant Plasmodium falciparum and Plasmodium vivax

Price, Ric N., Marfurt, Jutta, Chalfein, Ferryanto, Kenangalem, Enny, Piera, Kim A., Tjitra, Emiliana, Anstey, Nicholas M. and Russell, Bruce (2010). In vitro activity of pyronaridine against multidrug-resistant Plasmodium falciparum and Plasmodium vivax. Antimicrobial Agents and Chemotherapy,54(12):5146-5150.

Document type: Journal Article
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IRMA ID 81704288xPUB119
Title In vitro activity of pyronaridine against multidrug-resistant Plasmodium falciparum and Plasmodium vivax
Author Price, Ric N.
Marfurt, Jutta
Chalfein, Ferryanto
Kenangalem, Enny
Piera, Kim A.
Tjitra, Emiliana
Anstey, Nicholas M.
Russell, Bruce
Journal Name Antimicrobial Agents and Chemotherapy
Publication Date 2010
Volume Number 54
Issue Number 12
ISSN 0066-4804   (check CDU catalogue open catalogue search in new window)
Start Page 5146
End Page 5150
Total Pages 4
Place of Publication Washington, United States
Publisher American Society for Microbiology
Abstract Pyronaridine, a Mannich base antimalarial, has demonstrated high in vivo and in vitro efficacy against chloroquine-resistant Plasmodium falciparum. Although this drug has the potential to become a prominent artemisinin combination therapy, little is known about its efficacy against drug-resistant Plasmodium vivax. The in vitro antimalarial susceptibility of pyronaridine was assessed in multidrug-resistant P. vivax (n = 99) and P. falciparum (n = 90) isolates from Papua, Indonesia, using a schizont maturation assay. The median 50% inhibitory concentration (IC50) of pyronaridine was 1.92 nM (range, 0.24 to 13.8 nM) against P. falciparum and 2.58 nM (range, 0.13 to 43.6 nM) against P. vivax, with in vitro susceptibility correlating significantly with chloroquine, amodiaquine, and piperaquine (rs [Spearman's rank correlation coefficient] = 0.45 to 0.62; P < 0.001). P. falciparum parasites initially at trophozoite stage had higher IC50s of pyronaridine than those exposed at the ring stage (8.9 nM [range, 0.6 to 8.9 nM] versus 1.6 nM [range, 0.6 to 8.9 nM], respectively; P = 0.015), although this did not reach significance for P. vivax (4.7 nM [range, 1.4 to 18.7 nM] versus 2.5 nM [range, 1.4 to 15.6 nM], respectively; P = 0.085). The excellent in vitro efficacy of pyronaridine against both chloroquine-resistant P. vivax and P. falciparum highlights the suitability of the drug as a novel partner for artemisinin-based combination therapy in regions where the two species are coendemic.

DOI http://dx.doi.org/10.1128/AAC.00801-10   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)


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