咯萘啶和米帕林对12株恶性疟原虫的体外活性。

Activity of pyronaridine and mepacrine against twelve strains of Plasmodium falciparum in vitro.

作者信息

Elueze E I, Croft S L, Warhurst D C

机构信息

Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, UK.

出版信息

J Antimicrob Chemother. 1996 Mar;37(3):511-8. doi: 10.1093/jac/37.3.511.

DOI:10.1093/jac/37.3.511

PMID:9182108

Abstract

Pyronaridine, an acridine derivative, has been found effective in China for the treatment of drug-resistant falciparum malaria. The activities of pyronaridine and mepacrine were compared with those of standard antimalarial drugs in vitro against chloroquine-sensitive (CS) and chloroquine-resistant (CR) Plasmodium falciparum isolates to investigate cross resistance. The 50% inhibitory concentrations (IC(50)) against the resistant isolates were 2.8-fold higher than the sensitive isolates for pyronaridine (CS = 7.3 nM; CR = 20.5 nM) and 3.2-fold higher for mepacrine (CS = 13.3 nM; CR = 42.6 nM). These same isolates showed an 11-fold difference in sensitivity to chloroquine with mean IC(50) values of 21 nM for sensitive and 239 nM for resistant parasites. A significant correlation was observed between parasite sensitivity (IC(50)) to pyronaridine and the drugs, mepacrine, amodiaquine and chloroquine. However, the high level of activity seen with pyronaridine, even against the CR isolates, should encourage further field trials with this drug.

摘要

咯萘啶，一种吖啶衍生物，在中国已被发现对治疗抗药性恶性疟有效。在体外将咯萘啶和米帕林的活性与标准抗疟药物针对氯喹敏感（CS）和氯喹抗性（CR）恶性疟原虫分离株的活性进行比较，以研究交叉抗性。咯萘啶对抗性分离株的50%抑制浓度（IC(50)）比对敏感分离株高2.8倍（CS = 7.3 nM；CR = 20.5 nM），米帕林则高3.2倍（CS = 13.3 nM；CR = 42.6 nM）。这些相同的分离株对氯喹的敏感性差异达11倍，敏感寄生虫的平均IC(50)值为21 nM，抗性寄生虫为239 nM。观察到寄生虫对咯萘啶与米帕林、阿莫地喹和氯喹的敏感性（IC(50)）之间存在显著相关性。然而，咯萘啶所表现出的高活性，即使是针对CR分离株，也应促使对该药物进行进一步的现场试验。