In Vitro Sensitivity of Pyronaridine in Thai Isolates of .

Pyronaridine, a Mannich base antimalarial agent with a high activity against chloroquine-resistant , 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 . In addition, the influence of resistant genes concerning in vitro pyronaridine sensitivity was determined. The mean pyronaridine 50% inhibitory concentration (IC) of 118 parasite isolates was 5.6 ± 3.1 nM (range = 0.2-15.4 nM) with a significant positive correlation with artesunate IC ( = 0.246, = 0.008) and amodiaquine IC ( = 0.220, = 0.042) and a significant negative correlation with quinine IC ( = 0.185, = 0.047). Parasites containing the 86Y allele exhibited significantly reduced pyronaridine sensitivity compared with those with the N86 allele (7.6 ± 3.3 nM and 5.4 ± 3.0 nM, respectively, = 0.032, independent 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.