McCabe R E
Medical Service, Veterans Administration Medical Center, Martinez, California 94553.
J Parasitol. 1988 Oct;74(5):748-53.
Primaquine has been used to treat Chagas' disease in humans and has been reported to be active against extracellular Trypanosoma cruzi. Experiments were designed to evaluate the relative activity of primaquine against extra- and intracellular T. cruzi and to determine if primaquine might be combined advantageously with ketoconazole. Primaquine at 0.5 micrograms/ml significantly inhibited T. cruzi replication in infected mouse peritoneal macrophages and also effectively treated infected L929 cells. To examine the effect of primaquine on extracellular organisms, tissue culture T. cruzi were incubated with primaquine for different periods of time and then used to infect macrophages. Incubation with 10 micrograms/ml for 14 hr but not 8 hr significantly inhibited but did not eradicate replication. Incubation of spleen amastigotes or blood trypomastigotes for 2 hr with 10 micrograms/ml did not inhibit replication. Incubation of extracellular tissue culture T. cruzi with primaquine for 2 hr did not potentiate the activity of ketoconazole against intracellular organisms. The combination of primaquine and ketoconazole administered to acutely infected mice significantly decreased parasitemias in comparison to treatment with primaquine or ketoconazole alone. Thus primaquine acts primarily on intracellular rather than extracellular T. cruzi. Primaquine and ketoconazole appear to have additive activity in vivo.
伯氨喹已被用于治疗人类的恰加斯病，并且据报道对细胞外的克氏锥虫具有活性。设计实验以评估伯氨喹对细胞外和细胞内克氏锥虫的相对活性，并确定伯氨喹是否可以与酮康唑联合使用并取得有利效果。0.5微克/毫升的伯氨喹显著抑制感染小鼠腹腔巨噬细胞中的克氏锥虫复制，并且也有效地治疗了感染的L929细胞。为了研究伯氨喹对细胞外生物体的作用，将组织培养的克氏锥虫与伯氨喹孵育不同时间，然后用于感染巨噬细胞。用10微克/毫升孵育14小时而非8小时可显著抑制但不能根除复制。用10微克/毫升将脾无鞭毛体或血液锥鞭毛体孵育2小时不抑制复制。将细胞外组织培养的克氏锥虫与伯氨喹孵育2小时不会增强酮康唑对细胞内生物体的活性。与单独用伯氨喹或酮康唑治疗相比，给急性感染的小鼠施用伯氨喹和酮康唑的组合可显著降低寄生虫血症。因此，伯氨喹主要作用于细胞内而非细胞外的克氏锥虫。伯氨喹和酮康唑在体内似乎具有相加活性。
