In-vitro activity of pyronaridine and amodiaquine against African isolates (Senegal) of Plasmodium falciparum in comparison with standard antimalarial agents
In-vitro activity of pyronaridine and amodiaquine against African isolates (Senegal) of Plasmodium falciparum in comparison with standard antimalarial agents
复制标题
DOI：
10.1093/jac/42.3.333
复制
发表时间：
1998-09-01
影响因子：
5.2
通讯作者：
Doury, JC
中科院分区：
文献类型：
--
作者：
Pradines, B;Tall, A;Doury, JC
采用同位素、微量药敏试验等方法，研究了咯萘啶、阿莫地喹、氯喹和奎宁对来自塞内加尔的161株恶性疟原虫(Dielmo、Ndiop和Pikine)的体外抑菌作用。平均IC50值(50%抑制浓度)分别为3.8 nM(95%可信区间，3.1~4.4)和12.0 nM(95%CI，10.0~14.0 nM)。吡咯那定和阿莫地喹对敏感寄生虫的杀灭活性高于氯喹。然而，这两种药物对氯喹抗性菌株的活性(P<；0.002和P<；0.025)明显低于对氯喹敏感菌株的活性。根据现有数据的统计计算(平均IC50+2S.D.)，对咯萘啶的体外敏感性界值为IC50；15 NM；8株(5%)的IC50为>；15 NM。没有检测到的菌株对阿莫地喹(IC50>；80 NM)显示抗药性。体外交叉耐药相关分析显示，咯萘啶与氯喹(r(2)=0.19，P<；0.001)、咯萘啶与奎宁(r(2)=0.44，P<；0.001)、咯萘啶与阿莫地喹(P=0.34，P<；0.001)、阿莫地喹与氯喹(r(2)=0.14，P<；0.001)、阿莫地喹与奎宁(r(2)=0.21，P<；0.001)呈显著正相关。目前的体外研究结果需要与临床研究进行比较。
The in-vitro activities of pyronaridine, amodiaquine, chloroquine and quinine were evaluated against 161 isolates of Plasmodium falciparum from Senegal (Dielmo, Ndiop and Pikine), using an isotopic, micro, drug susceptibility test. The mean IC50 values (50% inhibitory concentration) for pyronaridine and amodiaquine were 3.8 nM (95% confidence interval (95% CI), 3.1-4.4) and 12.0 nM (95% CI, 10.0-14.0 nM), respectively. Pyronaridine and amodiaquine were more active than chloroquine against susceptible parasites. However, both drugs were significantly less active (P < 0.002 and P < 0.025) against chloroquine-resistant isolates than against chloroquine-susceptible isolates. Based on statistical calculation using the present data (mean IC50 + 2 S.D.), the cut-off value for in-vitro susceptibility to pyronaridine is IC50 < 15 nM; for eight isolates (5%) the IC50 was >15 nM. No isolates tested showed resistance to amodiaquine (IC50 > 80 nM). Significant positive correlations, suggesting cross-resistance among these drugs in vitro, were found between pyronaridine and chloroquine (r(2) = 0.19, P < 0.001), pyronaridine and quinine (r(2) = 0.44, P < 0.001), pyronaridine and amodiaquine (P = 0.34, P < 0.001), amodiaquine and chloroquine (r(2) = 0.14, P < 0.001), and amodiaquine and quinine (r(2) = 0.21, P < 0.001). The present in-vitro findings require comparison with clinical studies.