蒿甲醚和蒿乙醚在体外和体内对疟原虫的比较。

Comparison of beta-artemether and beta-arteether against malaria parasites in vitro and in vivo.

作者信息

Shmuklarsky M J, Klayman D L, Milhous W K, Kyle D E, Rossan R N, Ager A L, Tang D B, Heiffer M H, Canfield C J, Schuster B G

机构信息

Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC.

出版信息

Am J Trop Med Hyg. 1993 Mar;48(3):377-84. doi: 10.4269/ajtmh.1993.48.377.

DOI:10.4269/ajtmh.1993.48.377

PMID:8470775

Abstract

The antimalarial activity of beta-artemether and beta-arteether was compared in three test systems: in vitro against chloroquine-resistant and chloroquine-sensitive Plasmodium falciparum parasites, in mice infected with P. berghei, and in Aotus monkeys infected with chloroquine-resistant P. falciparum. In vitro, the mean 50% inhibitory concentration (IC50) for beta-artemether was 1.74 nM (range 1.34-1.81 nM), and this value for beta-arteether was 1.61 nM (range 1.57-1.92 nM). They were approximately 2.5-fold more potent than artemisinin, which had a mean IC50 of 4.11 nM (range 3.36-4.60 nM). In the mouse model, the 50% curative doses (CD50) of beta-artemether and beta-arteether had a mean value of 55 mg/kg (32-78 mg/kg). The 50% effective curative doses (ED50) in the Aotus monkey were 7.1 mg/kg (95% confidence interval [CI] = 3.7-13.5) for beta-artemether and 11.8 mg/kg (95% CI = 6.5-21.3) for beta-arteether. Overall, the activities of the two drugs were comparable.

摘要

在三个测试系统中比较了β-蒿甲醚和β-青蒿琥酯的抗疟活性：体外针对氯喹抗性和氯喹敏感性恶性疟原虫寄生虫、感染伯氏疟原虫的小鼠以及感染氯喹抗性恶性疟原虫的夜猴。在体外，β-蒿甲醚的平均50%抑制浓度（IC50）为1.74 nM（范围为1.34 - 1.81 nM），β-青蒿琥酯的该值为1.61 nM（范围为1.57 - 1.92 nM）。它们的效力比青蒿素高约2.5倍，青蒿素的平均IC50为4.11 nM（范围为3.36 - 4.60 nM）。在小鼠模型中，β-蒿甲醚和β-青蒿琥酯的50%治愈剂量（CD50）的平均值为55 mg/kg（32 - 78 mg/kg）。在夜猴中，β-蒿甲醚的50%有效治愈剂量（ED50）为7.1 mg/kg（95%置信区间[CI]=3.7 - 13.5），β-青蒿琥酯为11.8 mg/kg（95%CI = 6.5 - 21.3）。总体而言，两种药物的活性相当。