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Am J Trop Med Hyg. 2018 Jan;98(1):51-56. doi: 10.4269/ajtmh.17-0286. Epub 2018 Jan 1.

In Vitro Sensitivity of Pyronaridine in Thai Isolates of Plasmodium falciparum.

Author information

1
Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
2
Department of Parasitology, Phramongkutklao College of Medicine, Bangkok 10400, Thailand.

Abstract

Pyronaridine, a Mannich base antimalarial agent with a high activity against chloroquine-resistant Plasmodium falciparum, has been combined with artesunate as a new artemisinin based combination therapy (ACT). Pyronaridine-artesunate combination could be one of the choices for the treatment of uncomplicated falciparum malaria in multidrug-resistant areas including Thailand. The aim of this study was to determine in vitro sensitivity and cross-resistance pattern of pyronaridine in Thai isolates of P. falciparum. In addition, the influence of resistant genes concerning in vitro pyronaridine sensitivity was determined. The mean pyronaridine 50% inhibitory concentration (IC50) of 118 parasite isolates was 5.6 ± 3.1 nM (range = 0.2-15.4 nM) with a significant positive correlation with artesunate IC50 (r = 0.246, P = 0.008) and amodiaquine IC50 (r = 0.220, P = 0.042) and a significant negative correlation with quinine IC50 (r = -0.185, P = 0.047). Parasites containing the pfmdr1 86Y allele exhibited significantly reduced pyronaridine sensitivity compared with those with the pfmdr1 N86 allele (7.6 ± 3.3 nM and 5.4 ± 3.0 nM, respectively, P = 0.032, independent t test); however, the difference may not be clinically relevant. Pyronaridine-artesunate could be the candidate ACT to treat multidrug-resistant falciparum malaria in Thailand with careful monitoring.

PMID:
29141758
PMCID:
PMC5928699
DOI:
10.4269/ajtmh.17-0286
[Indexed for MEDLINE]
Free PMC Article

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