A COMPARISON OF THE INVITRO ACTIVITIES OF AMODIAQUINE AND DESETHYLAMODIAQUINE AGAINST ISOLATES OF PLASMODIUM-FALCIPARUM
A COMPARISON OF THE INVITRO ACTIVITIES OF AMODIAQUINE AND DESETHYLAMODIAQUINE AGAINST ISOLATES OF PLASMODIUM-FALCIPARUM
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DOI：
10.4269/ajtmh.1989.40.7
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发表时间：
1989-01-01
影响因子：
3.3
通讯作者：
DAVIDSON, DE
中科院分区：
文献类型：
--
作者：
CHILDS, GE;BOUDREAU, EF;DAVIDSON, DE
对 1985 年 10 月至 12 月从泰国东部收集的 35 株恶性疟原虫现场分离株评估了阿莫地喹（阿莫地喹、氯喹和甲氟喹的去乙基代谢物）的抗疟活性，以确定这些化合物之间的交叉耐药性模式。该测定系统基于裂殖体成熟的体外抑制。寄生虫通常对甲氟喹敏感（平均 50% 抑制浓度 = 9.98 nM），对氯喹高度耐药（IC50 = 313 nM）。去乙基阿莫地喹的平均体外活性 (67.5 nM) 比阿莫地喹 (18.2 nM) 的平均体外活性低约 3.5 倍。去乙基阿莫地喹和氯喹的IC50之间存在显着的排序相关性，但阿莫地喹和氯喹之间不存在显着的排序相关性，这表明临床研究中观察到的氯喹和阿莫地喹之间的明显交叉耐药性可能与氯喹和代谢物之间的交叉耐药性更密切相关，而不是氯喹和母体化合物之间的交叉耐药性。阿莫地喹 IC50 值 > 20 nM 的分离株表现出与去乙基阿莫地喹值高度相关；然而，不可能准确预测阿莫地喹 IC50 值< 20 nM 的分离株对去乙基阿莫地喹的敏感性。
The antimalarial activities of amodiaquine, the desethyl metabolite of amodiaquine, chloroquine, and mefloquine were evaluated against 35 field isolates of Plasmodium falciparum collected from eastern Thailand, October-December 1985, to define patterns of cross-resistance among these compounds. The assay system was based on the in vitro inhibition of schizont maturation. The parasites were generally sensitive to mefloquine (mean 50%-inhibitory concentrations = 9.98 nM) and highly resistant to chloroquine (IC50 = 313 nM). The mean in vitro activity of desethylamodiaquine (67.5 nM) was approximately 3.5 times lower than that of amodiaquine (18.2 nM). There was a significant rank-order correlation between the IC50s of desethylamodiaquine and chloroquine, but not between amodiaquine and chloroquine, which suggests that the apparent cross-resistance between chloroquine and amodiaquine observed in clinical studies may be more closely related to the cross-resistance between chloroquine and the metabolite rather than between chloroquine and the parent compound. Isolates with IC50 values of amodiaquine > 20 nM demonstrated a high degree of correlation with values of desethylamodiaquine; however, it was not possible to accurately predict the sensitivity to desethylamodiaquine of isolates which had IC50 values of amodiaquine of < 20 nM.