Global Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia.
Antimicrob Agents Chemother. 2010 Dec;54(12):5146-50. doi: 10.1128/AAC.00801-10. Epub 2010 Sep 27.
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 (IC(50)) 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 (r(s) [Spearman's rank correlation coefficient] = 0.45 to 0.62; P < 0.001). P. falciparum parasites initially at trophozoite stage had higher IC(50)s 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.
派隆那林是一种曼尼希碱抗疟药，对耐氯喹的恶性疟原虫具有很高的体内和体外疗效。尽管该药有可能成为一种突出的青蒿素联合疗法，但人们对其治疗耐多药间日疟原虫的疗效知之甚少。采用裂殖体成熟试验，评估了派隆那林对来自印度尼西亚巴布亚的多药耐药间日疟原虫（n = 99）和恶性疟原虫（n = 90）分离株的体外抗疟活性。恶性疟原虫和间日疟原虫的半数抑制浓度（IC 50 ）的中位数分别为 1.92 nM（范围为 0.24 至 13.8 nM）和 2.58 nM（范围为 0.13 至 43.6 nM），体外敏感性与氯喹、阿莫地喹和哌喹显著相关（r s [Spearman 秩相关系数] = 0.45 至 0.62；P < 0.001）。处于滋养体期的恶性疟原虫寄生虫对派隆那林的 IC 50 高于处于环状期的寄生虫（分别为 8.9 nM[范围为 0.6 至 8.9 nM]和 1.6 nM[范围为 0.6 至 8.9 nM]；P = 0.015），但对于间日疟原虫，这种差异没有达到统计学意义（分别为 4.7 nM[范围为 1.4 至 18.7 nM]和 2.5 nM[范围为 1.4 至 15.6 nM]；P = 0.085）。派隆那林对耐氯喹的间日疟原虫和恶性疟原虫均具有极好的体外疗效，这突出表明该药物适合作为在两种寄生虫同时流行的地区以青蒿素为基础的联合治疗的新伙伴。
