Division of Parasitology, Central Drug Research Institute (CSIR), Chattar Manzil Palace, M.G. Road, Lucknow, 226001, Uttar Pradesh, India.
Parasitol Res. 2011 Apr;108(4):793-800. doi: 10.1007/s00436-010-2230-2. Epub 2011 Jan 7.
The chemotherapy of visceral leishmaniasis (VL) has several limitations including resistance and toxicity of the existing drugs. Downregulation of immune system further aggravates the problems. To combat this situation, leishmanicidal efficacy of already marketed standard antifungal drug, fluconazole under the approach of "therapeutic switching" in combination with standard antileishmanial drug, miltefosine, and a potent immunomodulator agent, picroliv, were evaluated in hamsters infected with Leishmania donovani. Animals treated with fluconazole (50 mg/kg × 5 days, oral (p.o.)) + miltefosine (5 mg/kg × 5 days, p.o.) showed enhancement in antileishmanial efficacy (77%), reactive nitrogen species, reactive oxygen species, hydrogen peroxide, and phagocytosis index as compared to those treated with individual drugs. Addition of picroliv to this combination further increased the antileishmanial efficacy from 77% to 88%. Upregulation of cell-mediated immunity was also observed in animals of this group which strengthens the immunomodulatory role of picroliv. These findings suggest a new option for antileishmanial chemotherapy at lower cost and toxicity.
内脏利什曼病（VL）的化疗存在多种局限性，包括现有药物的耐药性和毒性。免疫系统的下调进一步加剧了这些问题。为了应对这种情况，在“治疗转换”的方法下，评估了已经上市的标准抗真菌药物氟康唑联合标准抗利什曼病药物米替福新和一种有效的免疫调节剂吡咯利夫在感染利什曼原虫的仓鼠中的杀利什曼原虫功效。与单独使用药物相比，用氟康唑（50mg/kg×5 天，口服（p.o.））+米替福新（5mg/kg×5 天，p.o.）治疗的动物显示出增强的抗利什曼原虫功效（77%）、活性氮物质、活性氧物质、过氧化氢和吞噬指数。将吡咯利夫添加到该组合中，可将抗利什曼原虫功效从 77%进一步提高到 88%。该组动物的细胞介导免疫也得到上调，这增强了吡咯利夫的免疫调节作用。这些发现为降低成本和毒性的抗利什曼病化疗提供了一种新的选择。
