磷酸萘酚喹与青蒿素伍用增效和延缓疟原虫抗药性的研究

STUDY OF SYNERGETIC EFFECT OF NAPHTHOQUINE PHOSPHATE AND ITS COMBINATION WITH ARTEMISININ AND ITS DELAYING EFFECT ON DRUG-RESISTANCE OF PLASMODIUM BERGHEI

本文采用鼠疟模型进行磷酸萘酚喹与青蒿素伍用的药效学研究。用正交设计和4天抑制试验法,研究两药伍用增效的最适配比。采用药物剂量递增培育抗性的方法,连续血传100代,分别培育鼠疟原虫对磷酸萘酚喹、青蒿素及两药伍用的抗药性。结果显示磷酸萘酚喹和青蒿素最适配比为1∶50,对鼠疟敏感株和抗氯喹株的增效指数分别为4.2和8.2,杀虫速度和治愈率均优于单药。培育至100代时,磷酸萘酚喹、青蒿素和两药伍用抗性指数分别为200.3、5.6和4.4。结果表明,磷酸萘酚喹与青蒿素配伍具有增效作用,并能明显延缓疟原虫对单药抗性产生的速度,降低抗性水平。

To study the pharmacodynamic effect of naphthoquine phosphate and its combination with artemisinin in mice infected with Plasmodium berghei. Applying orthogonal design and ＂4 d suppressive test＂ to study the optimum proportion of synergetic effect. By gradually increasing drug pressure during successive weekly passages of P. berghei infection in mice, cultivate drug- resistance of P. berghei to naphthoquine phosphate, artemisinin and its combination respectively, up to 100 passages. The optimum proportion of naphthoquine phosphate and artemisinin was 1 ： 50. The pharmacodynamic tests revealed that the combination of these two drugs was synergetic, the synergetic indices were 4.2 and 8.2 that calculated from chloroquine-sensitive strain of P. bergher or chloroquine-res%tent strain of P. bergher, respectively. The curative effects of the combination against P. bergher in mice were superior to the drug used in single. After 100 passages, the resistant indices of naphthoquine phosphate, artemisinin and the combination were 200.3, 5.6 and 4.4 respectively. The tests confirmed that the naphthoquine phosphate and its combination with artemisinin exhibited a synergetic activity against P. bergher in mice. It was also revealed that the combination could delay the emergence of drug resistance and reduce its resistance level.