Gangneux J P, Sulahian A, Garin Y J, Farinotti R, Derouin F
Laboratoire de Parasitologie-Mycologie, Faculté de Médecine Lariboisière-Saint-Louis, Paris, France.
Antimicrob Agents Chemother. 1996 May;40(5):1214-8. doi: 10.1128/AAC.40.5.1214.
The tolerance and efficacy of amphotericin B (AmB) deoxycholate (Fungizone) were compared with those of liposomal AmB (AmBisome) in a murine model of visceral leishmaniasis induced by Leishmania infantum. Control groups consisted of untreated mice and mice treated with a pentavalent antimonial (Glucantime). BALB/c mice were infected intravenously on day 0 with 10(7) promastigotes of L. infantum and then treated from day 7 to 17 (early treatment group) or from day 60 to 70 (delayed treatment group). The pentavalent antimonial was administered daily by intraperitoneal injection, whereas AmB formulations were administered intravenously on alternate days. On days 20, 60, and 120 (early treatment group) and on days 72 and 125 (delayed treatment group), parasite burdens in the liver, spleen, and lungs were determined by subculturings using a microtitration method. A dose range study showed that administration of AmBisome at the well-tolerated doses of 5 or 50 mg/kg of body weight completely eradicated the parasites from the tissues. At 0.8 mg/kg, AmBisome proved more efficacious than AmB deoxycholate administered at the same dose. We also compared the levels of AmB deoxycholate and AmBisome in plasma and tissue. Mice treated with AmBisome had levels of AmB in tissue much higher than did AmB deoxycholate-treated mice with persistent detectable levels 14 weeks after treatment. These results seem to account for the remarkable efficacy of the liposomal formulation of AmB in the treatment of visceral leishmaniasis due to L. infantum.
在由婴儿利什曼原虫引起的内脏利什曼病小鼠模型中，比较了两性霉素B（AmB）脱氧胆酸盐（两性霉素B注射剂）和脂质体AmB（安必素）的耐受性和疗效。对照组包括未治疗的小鼠和用五价锑剂（葡糖酸锑钠）治疗的小鼠。BALB/c小鼠在第0天静脉注射10⁷个婴儿利什曼原虫前鞭毛体，然后在第7天至第17天（早期治疗组）或第60天至第70天（延迟治疗组）进行治疗。五价锑剂通过腹腔注射每日给药，而AmB制剂隔日静脉给药。在第20天、第60天和第120天（早期治疗组）以及第72天和第125天（延迟治疗组），通过微量滴定法传代培养来测定肝脏、脾脏和肺部的寄生虫负荷。剂量范围研究表明，以5或50mg/kg体重的耐受性良好的剂量给予安必素可完全消除组织中的寄生虫。在0.8mg/kg时，安必素比以相同剂量给药的两性霉素B脱氧胆酸盐更有效。我们还比较了血浆和组织中两性霉素B脱氧胆酸盐和安必素的水平。用安必素治疗的小鼠组织中的AmB水平比用两性霉素B脱氧胆酸盐治疗的小鼠高得多，治疗后14周仍可检测到持续水平。这些结果似乎可以解释脂质体AmB制剂在治疗婴儿利什曼原虫引起的内脏利什曼病方面的显著疗效。
