Awadzi K, Edwards G, Opoku N O, Ardrey A E, Favager S, Addy E T, Attah S K, Yamuah L K, Quartey B T
Onchocerciasis Chemotherapy Research Centre (OCRC), Hohoe Hospital, P. O. Box 144, Hohoe, Ghana.
Ann Trop Med Parasitol. 2004 Sep;98(6):595-614. doi: 10.1179/000349804225021370.
Two randomized, double-blind, placebo-controlled trials, in which levamisole (2.5 mg/kg) was given alone or co-administered with ivermectin (200 microg/kg) or albendazole (400 mg), were conducted. In Trial 1, safety and drug-drug interaction were explored in 42 healthy male volunteers. During Trial 2, the safety of the same treatment regimens and their efficacy against the adult worms and microfilariae of Onchocerca volvulus were investigated in 66 infected subjects of both sexes. Safety was determined from the results of detailed clinical and laboratory examinations before treatment, during hospitalization and on day 30. The pharmacokinetic parameters for levamisole alone and the combinations were determined in Trial 1 and then compared with historical data for ivermectin and albendazole, given as single agents, to determine if drug-drug interaction had occurred. The level of efficacy against the adult worms was determined by the examination of histology sections of nodules excised 6 months posttreatment and from the changes seen in the levels of microfilaridermia within a year of treatment. Microfilaricidal efficacy was estimated from the reductions in the levels of microfilaridermia between day 0 (1 day pre-treatment) and day 30. Although the regimens were generally well tolerated, there were unexpected adverse effects in both healthy volunteers and infected subjects. Clinically significant drug-drug interactions resulted in an increase in the bio-availability of ivermectin but a reduction in that of albendazole when these drugs were co-administered with levamisole. Levamisole given alone or with albendazole had little effect on O. volvulus. The combination of levamisole with ivermectin was neither macrofilaricidal nor more effective against the microfilariae and the adult worms than ivermectin alone. The pathogenesis of the adverse events and the drug-drug interactions are discussed.
进行了两项随机、双盲、安慰剂对照试验，其中左旋咪唑（2.5毫克/千克）单独给药，或与伊维菌素（200微克/千克）或阿苯达唑（400毫克）联合给药。在试验1中，对42名健康男性志愿者进行了安全性和药物相互作用的研究。在试验2中，对66名男女感染者进行了相同治疗方案的安全性及其对盘尾丝虫成虫和微丝蚴疗效的研究。根据治疗前、住院期间和第30天详细的临床和实验室检查结果确定安全性。在试验1中测定了左旋咪唑单独使用及联合用药的药代动力学参数，然后与伊维菌素和阿苯达唑单药使用的历史数据进行比较，以确定是否发生了药物相互作用。通过检查治疗后6个月切除的结节组织学切片以及治疗后一年内微丝蚴血症水平的变化来确定对成虫的疗效水平。根据第0天（治疗前1天）和第30天微丝蚴血症水平的降低情况估算杀微丝蚴疗效。虽然这些方案总体耐受性良好，但健康志愿者和感染者均出现了意外不良反应。当这些药物与左旋咪唑联合使用时，具有临床意义的药物相互作用导致伊维菌素的生物利用度增加，但阿苯达唑的生物利用度降低。单独使用左旋咪唑或与阿苯达唑联合使用对盘尾丝虫几乎没有作用。左旋咪唑与伊维菌素联合使用对成虫既无杀成虫作用，对微丝蚴的效果也不比单独使用伊维菌素更有效。本文讨论了不良事件的发病机制和药物相互作用。
