Shi X H, Shao B R, Ye X Y
Institute of Parasitic Diseases, Chinese Academy of Preventive Medicine, Shanghai.
Zhongguo Yao Li Xue Bao. 1990 Jan;11(1):66-9.
Pyronaridine, a highly effective antimalarial drug, was synthesized and developed by this institute. In order to test whether the joint blood schizontocidal action of pyronaridine (PND) and 2:1 mixture of sulfadoxine/pyrimethamine (SP) resulted in a potentiation or an additive effect, groups of P berghei ANKA strain-infected mice were treated with various single oral doses of PND and SP. Thin blood smears were made after 72 h and the parasitemia-negative rates were calculated. The ED50 values obtained were plotted in isobolograms. An additive action of this triple combination was demonstrated. Mice were inoculated with P berghei ANKA strain-infected erythrocytes 3 and 2 d after the mice were given a single oral dose of PND 10 mg/kg alone, or combined with SP 3 mg/kg. Thin blood smears made on d 3, 5, 8 and 10 revealed that the parasitemia-positive rates and the duration of residual blood schizontocidal action of PND used alone was similar to that of PND used in combination (P greater than 0.05). Three groups of mice carrying P berghei ANKA strain gametocytes were administered orally with pyrimethamine 0.1 mg/kg, SP 0.3 mg/kg and SP 0.3 mg/kg plus PND 0.5 mg/kg, respectively. Anopheles stephensi were then fed on the mice 2 h after the medication. There resulted no significant differences of gametocytocidal and sporontocidal effects among the 3 groups, since the oocyst-positive rate and the glandpositive rate were similar in these groups.
咯萘啶是一种高效抗疟药,由本研究所合成并研制。为了测试咯萘啶(PND)与周效磺胺/乙胺嘧啶(SP)2:1混合物的联合灭血裂殖体作用是产生增效还是相加作用,将伯氏疟原虫ANKA株感染的小鼠分组,给予不同单次口服剂量的PND和SP。72小时后制作薄血涂片并计算疟原虫血症阴性率。将获得的半数有效剂量(ED50)值绘制在等效线图上。结果表明该三联组合具有相加作用。给小鼠单次口服10mg/kg的PND,单独使用或与3mg/kg的SP联合使用,在给药后3天和2天接种伯氏疟原虫ANKA株感染的红细胞。在第3、5、8和10天制作的薄血涂片显示,单独使用PND的疟原虫血症阳性率和残余血裂殖体杀灭作用持续时间与联合使用PND时相似(P>0.05)。三组携带伯氏疟原虫ANKA株配子体的小鼠分别口服0.1mg/kg的乙胺嘧啶、0.3mg/kg的SP和0.3mg/kg的SP加0.5mg/kg的PND。给药2小时后,让斯氏按蚊叮咬这些小鼠。这三组之间的杀配子体和杀孢子体效果没有显著差异,因为这些组的卵囊阳性率和腺阳性率相似。