Mullen A B, Baillie A J, Carter K C
Departments of Pharmaceutical Sciences, University of Strathclyde, Glasgow, United Kingdom.
Antimicrob Agents Chemother. 1998 Oct;42(10):2722-5. doi: 10.1128/AAC.42.10.2722.
In this study, treatment efficacies of a nonionic surfactant vesicle formulation of sodium stibogluconate (SSG-NIV) and of several formulations of amphotericin B were compared in a murine model of visceral leishmaniasis. Treatment with multiple doses of AmBisome, Abelcet, and Amphocil (total dose, 12.5 mg of amphotericin B/kg of body weight) resulted in a significant suppression of parasite burdens in liver (P < 0.0005) and spleen (P < 0.0005) compared with those of controls, with Abelcet having the lowest activity. Only AmBisome and Amphocil gave significant suppression of parasites in bone marrow (compared to control values, P < 0.005). In the acute-infection model, single-dose treatments of SSG-NIV (296 mg of SbV/kg), SSG solution (296 mg of SbV/kg), or AmBisome (8 mg of amphotericin B/kg) were equally effective against liver parasites (compared to control values, P < 0.0005). SSG-NIV and AmBisome treatment also significantly suppressed parasites in bone marrow and spleen (P < 0.005), with SSG-NIV treatment being more suppressive (>98% suppression in all three sites). Free-SSG treatment failed to suppress spleen or bone marrow parasites. Infection status influenced treatment outcome. In the chronic-infection model, the AmBisome single-dose treatment was less effective in all three infection sites and the SSG-NIV single-dose treatment was less effective in the spleen. The results of this study suggest that the antileishmanial efficacy of SSG-NIV compares favorably with those of the novel amphotericin B formulations.
在本研究中，在内脏利什曼病小鼠模型中比较了葡萄糖酸锑钠非离子表面活性剂囊泡制剂（SSG-NIV）和几种两性霉素B制剂的治疗效果。用多剂量的安必素、两性霉素B脂质体和两性霉素B胶体分散体（总剂量，12.5mg两性霉素B/kg体重）进行治疗，与对照组相比，肝脏（P<0.0005）和脾脏（P<0.0005）中的寄生虫负荷得到显著抑制，两性霉素B脂质体的活性最低。只有安必素和两性霉素B胶体分散体对骨髓中的寄生虫有显著抑制作用（与对照值相比，P<0.005）。在急性感染模型中，SSG-NIV（296mg SbV/kg）、SSG溶液（296mg SbV/kg）或安必素（8mg两性霉素B/kg）的单剂量治疗对肝脏寄生虫同样有效（与对照值相比，P<0.0005）。SSG-NIV和安必素治疗也显著抑制了骨髓和脾脏中的寄生虫（P<0.005），其中SSG-NIV治疗的抑制作用更强（在所有三个部位的抑制率均>98%）。游离SSG治疗未能抑制脾脏或骨髓中的寄生虫。感染状态影响治疗结果。在慢性感染模型中，安必素单剂量治疗在所有三个感染部位的效果较差，而SSG-NIV单剂量治疗在脾脏中的效果较差。本研究结果表明，SSG-NIV的抗利什曼原虫疗效与新型两性霉素B制剂相当。
