Human African trypanosomiasis: Potential therapeutic benefits of an alternative suramin and melarsoprol regimen
Human African trypanosomiasis: Potential therapeutic benefits of an alternative suramin and melarsoprol regimen
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DOI：
10.1016/s1383-5769(02)00044-2
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发表时间：
2002-12-01
影响因子：
1.9
通讯作者：
Murray, M
中科院分区：
文献类型：
--
作者：
Jennings, FW;Rodgers, J;Murray, M
晚期人类非洲锥虫病的治疗因中枢神经系统(CNS)内锥虫的存在而变得复杂。通常用于治疗中枢神经系统疾病的处方包括使用杀锥虫药物苏拉明和美拉索。苏拉明不能有效地穿过血脑屏障，因此，在正常剂量下，不能治愈中枢神经系统阶段的感染。使用苏拉明进行初步治疗，以消除周围组织中的寄生虫。之后是静脉注射美拉索洛尔，它可以进入中枢神经系统。然而，美拉索洛尔不仅会产生严重的不良反应，而且使用起来也非常痛苦。帮助缓解这些问题的一个可能的方法是减少治疗方案中美拉索的总量。这项研究表明苏拉明和美拉索尔之间有协同作用，并表明单次注射苏拉明20 mg/kg，然后几乎立即外用0.05毫升(4.5摩尔)美拉索洛尔就可以治愈实验性的小鼠中枢神经系统锥虫病。当这些剂量作为单一疗法使用时，不会治愈感染。此外，给药的时机似乎对该方案的成功结果至关重要。如果注射苏拉明和外用美拉索前列醇之间的间隔从15分钟延长到3或7天，感染就不会痊愈。尽管与单一疗法相比，这些方案会延长复发时间。因此，有强有力的证据表明，注射苏拉明和外用美拉索前列醇应该几乎同时给予，以实现这两种药物的最有效组合。(C)2002爱思唯尔科学爱尔兰有限公司。保留所有权利。
Treatment of late-stage human African trypanosomiasis is complicated by the presence of trypanosomes within the central nervous system (CNS). The regimen commonly prescribed to treat CNS-stage disease involves the use of the trypanocidal drugs suramin and melarsoprol. Suramin does not cross the blood-brain barrier efficiently and therefore, at normal dosages, will not cure CNS-stage infections. An initial treatment with suramin is given to eliminate the parasites from the peripheral tissues. This is followed by a course of intravenous melarsoprol, which can enter the CNS. However, melarsoprol not only produces severe adverse reactions but also is extremely painful to administer. One possible method to help alleviate these problems is to reduce the total amount of melarsoprol in the treatment regimen. This study indicates a synergism between suramin and melarsoprol and demonstrates that experimental murine CNS-trypanosomiasis can be cured with a single intraperitoneal dose of 20 mg/kg suramin followed almost immediately by 0.05 ml (4.5 mumol) topical melarsoprol. These dosages will not cure the infection when administered as monotherapies. Moreover, the timing of the drug administration appears to be crucial to the successful outcome of the regimen. If the interval between injection of suramin and application of topical melarsoprol is extended from 15 min to 3 or 7 days, the infections are not cured. Although extended relapse times occur following these regimens when compared with monotherapy approaches. Thus, there is strong evidence that injected suramin and topical melarsoprol should be given almost simultaneously to achieve the most effective combination of the two drugs. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.