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In Vitro Sensitivity of Pyronaridine in Thai Isolates of Plasmodium falciparum

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

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.

Author Notes

Address correspondence to Mathirut Mungthin, Department of Parasitology, Phramongkutklao College of Medicine, Ratchawithi Rd., Bangkok 10400, Thailand. E-mail: mathirut@hotmail.com

Financial support: This study was financially supported by the Health System Research Institute/National Science and Technology Development Agency (P-13-50112), the Phramongkutklao Research Fund, and the Science Achievement Scholarship of Thailand.

Authors’ addresses: Kittiya Mahotorn, Peerapan Tan-ariya, and Thunyapit Thita, Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand, E-mails: k.mahotorn@gmail.com, peerapan.tan@mahidol.ac.th, and aomay_ao@hotmail.com. Toon Ruang-areerate, Naruemon Sitthichot, Nantana Suwandittakul, and Mathirut Mungthin, Department of Parasitology, Phramongkutklao College of Medicine, Bangkok 10400, Thailand, E-mails: youangtr@yahoo.com, mude_143@hotmail.com, suwanna_b@hotmail.com, and mathirut@hotmail.com.

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