Visceral leishmaniasis in the BALB/c mouse: a comparison of the efficacy of a nonionic surfactant formulation of sodium stibogluconate with those of three proprietary formulations of amphotericin B.
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.
Mullen
A B
AB
Departments of Pharmaceutical Sciences, University of Strathclyde, Glasgow, United Kingdom.
Baillie
A J
AJ
Carter
K C
KC
D000208:Acute Disease; D000666:Amphotericin B / Q000008:administration & dosage*; D000818:Animals; D000967:Antimony Sodium Gluconate / Q000008:administration & dosage*; D000981:Antiprotozoal Agents / Q000008:administration & dosage*; D002908:Chronic Disease; D005260:Female; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013501:Surface-Active Agents / Q000008:administration & dosage*
D000981:Antiprotozoal Agents; D013501:Surface-Active Agents; D000666:Amphotericin B; D000967:Antimony Sodium Gluconate