Jennings F W, Atouguia J M, Murray M
Department of Veterinary Parasitology, University of Glasgow, UK.
Trop Med Int Health. 1996 Oct;1(5):590-8. doi: 10.1111/j.1365-3156.1996.tb00084.x.
The 5-nitroimidazoles, MK-436 and fexinidazole dissolved in dimethylsulphoxide can be converted by the addition of hydroxypropylcellulose into gels which facilitates the ease and accuracy of administration. When these gels are used in combination with melarsoprol gel they are capable of curing experimental murine CNS-trypanosomiasis with a one-day treatment. The use of melarsoprol/MK-436 was more efficient than melarsoprol/fexinidazole gels. Thus while a single treatment with 0.1 ml 3.6% melarsoprol gel with 0.1 ml (14.3 mumol) fexinidazole gel cured the infected mice, the same dose of melarsoprol gel with 0.1 ml (4.0 mumol) of MK-436 gel was equally effective. It was also possible to prepare a combined melarsoprol/MK-436 gel which cured experimental CNS-trypanosomiasis with a single treatment. Topical treatment with this melarsoprol/MK-436 gel mixture also resolved clinically the hind leg paralysis which is associated with post-treatment reactive encephalopathy caused by non-curative treatment of CNS-trypanosomiasis.
溶解于二甲基亚砜中的5-硝基咪唑类药物MK-436和非昔硝唑，加入羟丙基纤维素后可转化为凝胶，这有助于给药的简便性和准确性。当这些凝胶与美拉胂醇凝胶联合使用时，它们能够通过一天的治疗治愈实验性小鼠中枢神经系统锥虫病。使用美拉胂醇/MK-436比美拉胂醇/非昔硝唑凝胶更有效。因此，用0.1毫升3.6%的美拉胂醇凝胶与0.1毫升（14.3微摩尔）非昔硝唑凝胶进行单次治疗可治愈感染小鼠，相同剂量的美拉胂醇凝胶与0.1毫升（4.0微摩尔）MK-436凝胶同样有效。还可以制备一种联合的美拉胂醇/MK-436凝胶，单次治疗即可治愈实验性中枢神经系统锥虫病。用这种美拉胂醇/MK-436凝胶混合物进行局部治疗，在临床上也解决了与中枢神经系统锥虫病非治愈性治疗引起的治疗后反应性脑病相关的后腿麻痹问题。
