Gaur R L, Dixit S, Sahoo M K, Khanna M, Singh S, Murthy P K
Division of Parasitology, Central Drug Research Institute, Lucknow, 226001, India.
Parasitology. 2007 Apr;134(Pt 4):537-44. doi: 10.1017/S0031182006001612. Epub 2006 Nov 2.
The study was aimed at developing better orally active albendazole (ALB) formulations. Six formulations (ALB-1 to ALB-6) were prepared and tested against Brugia malayi in Mastomys coucha and jird (Meriones unguiculatus) at 200 mg/kg, orally, for 5 consecutive days. The anti-filarial efficacy was assessed against microfilariae (mf), adult worms and female reproductive potential. Three of the 6 ALB formulations showed greatly improved female worm sterilizing potential (ALB-1: 90%; ALB-3: 63%; ALB-4: 77% of untreated control) in B. malayi - M. coucha model. Sterilization efficacy of ALB-1 was also better than that shown by pure-ALB (P<0.001) or its marketed tablet formulation, Zentel (P<0.01), while that of ALB-4 was better than pure-ALB (P<0.05). The activity of ALB-3, pure-ALB and Zentel was, however, comparable. ALB-1 also showed late microfilaricidal activity with a maximum of 78% fall in microfilarial count. In contrast, neither the pure ALB nor Zentel showed any microfilaricidal activity. In the jird - B. malayi model, ALB-1 and ALB-4 showed marginal sterilizing efficacy whereas pure ALB or Zentel were ineffective. In conclusion the anti-filarial efficacy of ALB-1 was found to be superior to pure-ALB or Zentel.
该研究旨在开发更好的口服活性阿苯达唑(ALB)制剂。制备了六种制剂(ALB-1至ALB-6),并以200mg/kg的剂量口服给药,连续5天,在多乳鼠和沙鼠(长爪沙鼠)体内针对马来布鲁线虫进行测试。评估了对微丝蚴(mf)、成虫和雌虫生殖潜能的抗丝虫功效。在马来布鲁线虫-多乳鼠模型中,6种ALB制剂中的3种显示出雌虫绝育潜能有显著提高(ALB-1:90%;ALB-3:63%;ALB-4:未治疗对照组的77%)。ALB-1的绝育功效也优于纯阿苯达唑(P<0.001)或其市售片剂肠虫清(P<0.01),而ALB-4的绝育功效优于纯阿苯达唑(P<0.05)。然而,ALB-3、纯阿苯达唑和肠虫清的活性相当。ALB-1还显示出晚期杀微丝蚴活性,微丝蚴计数最多下降78%。相比之下,纯阿苯达唑和肠虫清均未显示出任何杀微丝蚴活性。在沙鼠-马来布鲁线虫模型中,ALB-1和ALB-4显示出轻微的绝育功效,而纯阿苯达唑或肠虫清则无效。总之,发现ALB-1的抗丝虫功效优于纯阿苯达唑或肠虫清。