Coutinho A D, Dreyer G, Medeiros Z, Lopes E, Machado G, Galdino E, Rizzo J A, Andrade L D, Rocha A, Moura I
Centro de Pesquisas Aggeu Magalhaes, Fiocruz, Recife, Brazil.
Am J Trop Med Hyg. 1994 Mar;50(3):339-48. doi: 10.4269/ajtmh.1994.50.339.
To determine the effectiveness of single oral dosages of ivermectin ranging between 20 and 200 micrograms/kg and to make detailed observations of both the kinetics of parasite killing and the adverse reactions induced by treatment, the present double-blind study on ivermectin treatment of lymphatic filariasis caused by Wuchereria bancrofti was undertaken with 43 microfilaremic patients in Recife, Brazil. Follow-up at one year indicated equivalent efficacy for the 20-, 100-, and 200-micrograms/kg drug dosages in reducing microfilaremia to geometric means of 13-25% of pretreatment levels. Adverse clinical reactions (predominantly fever, headache, weakness, and myalgia) occurred to some degree in almost all patients but generally lasted only 24-48 hr and were easily managed symptomatically. Adverse reactions were significantly milder in those receiving the lowest (20 micrograms/kg) ivermectin dose, and they were significantly correlated with individuals' pretreatment microfilaremia levels in all groups. Posttreatment eosinophilia was a regular feature of the response to treatment, with the magnitude and kinetics also proportional to pretreatment microfilarial levels. Transient pulmonary function abnormalities (16 of 42, 38%), liver enzyme elevations (10 of 43, 23%), and hematuria (9 of 42, 22%) developed posttreatment, but all cleared without significant complications. The results indicate that W. bancrofti from Brazil is similar to strains of the parasites studied elsewhere in susceptibility to ivermectin, that the drug's systemic adverse reactions are essentially those resulting from parasite clearance, and that the intensity of these reactions can be significantly reduced by using the low (20 micrograms/kg) dose of ivermectin. This detailed dose-finding study provides information necessary for developing optimal regimens to treat bancroftian filariasis with ivermectin either alone or in combination with other medications.
为了确定20至200微克/千克之间单次口服伊维菌素剂量的有效性,并详细观察寄生虫杀灭动力学和治疗引起的不良反应,在巴西累西腓对43名微丝蚴血症患者进行了本次关于伊维菌素治疗班氏吴策线虫引起的淋巴丝虫病的双盲研究。一年的随访表明,20微克/千克、100微克/千克和200微克/千克的药物剂量在将微丝蚴血症降低至治疗前水平的几何平均值的13%-25%方面具有同等疗效。几乎所有患者都在一定程度上出现了不良临床反应(主要是发热、头痛、虚弱和肌痛),但通常仅持续24-48小时,且通过对症治疗易于处理。接受最低(20微克/千克)伊维菌素剂量的患者的不良反应明显较轻,并且在所有组中,不良反应与个体治疗前的微丝蚴血症水平显著相关。治疗后嗜酸性粒细胞增多是治疗反应的一个常见特征,其程度和动力学也与治疗前的微丝蚴水平成比例。治疗后出现了短暂的肺功能异常(42例中的16例,38%)、肝酶升高(43例中的10例,23%)和血尿(42例中的9例,22%),但所有这些都在没有明显并发症的情况下恢复正常。结果表明,巴西的班氏吴策线虫在对伊维菌素的敏感性方面与在其他地方研究的寄生虫菌株相似,该药物的全身不良反应基本上是由寄生虫清除引起的,并且通过使用低剂量(20微克/千克)的伊维菌素可以显著降低这些反应的强度。这项详细的剂量探索研究为制定单独使用伊维菌素或与其他药物联合治疗班氏丝虫病的最佳方案提供了必要信息。