Department of Immunology and Infection, Faculty of Infectious Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Pharmidex, Stevenage Bioscience Catalyst, Stevenage, UK.
Int J Antimicrob Agents. 2017 Aug;50(2):203-209. doi: 10.1016/j.ijantimicag.2017.01.038. Epub 2017 May 25.
Human African trypanosomiasis (HAT) is a neglected tropical disease, with a population of 70 million at risk. Current treatment options are limited. In the search for new therapeutics, the repurposing of the broad-spectrum antiprotozoal drug fexinidazole has completed Phase III trials with the anticipation that it will be the first oral treatment for HAT. This study used the recently validated bioluminescence imaging model to assess the dose and rate of kill effect of fexinidazole in infected mice, and the dose-dependent effect of fexinidazole on trypanosome infection. Pharmacokinetics of fexinidazole in plasma and central nervous system (CNS) compartments were similar in both infected and uninfected mice. Drug distribution within the CNS was further examined by microdialysis, showing similar levels in the cortex and hippocampus. However, high variability in drug distribution and exposure was found between mice.
人类非洲锥虫病（HAT）是一种被忽视的热带病，有 7000 万人处于危险之中。目前的治疗选择有限。在寻找新的治疗方法时，广谱抗原生动物药物非昔硝唑的重新定位已经完成了 III 期临床试验，预计它将成为治疗 HAT 的第一种口服药物。本研究使用最近验证的生物发光成像模型来评估感染小鼠中非昔硝唑的剂量和杀伤效果，以及非昔硝唑对锥虫感染的剂量依赖性作用。感染和未感染小鼠的非昔硝唑在血浆和中枢神经系统（CNS）隔室中的药代动力学相似。然而，在小鼠之间发现药物分布和暴露的变异性很大。
