Efficacies of vesicular and free sodium stibogluconate formulations against clinical isolates of Leishmania donovani

被引:22
作者
Carter, KC
Mullen, AB
Sundar, S
Kenney, RT
机构
[1] Univ Strathclyde, Dept Immunol, Glasgow G4 ONR, Lanark, Scotland
[2] Univ Strathclyde, Dept Pharmaceut Sci, Glasgow G4 ONR, Lanark, Scotland
[3] Banaras Hindu Univ, Inst Med Sci, Varanasi 221005, Uttar Pradesh, India
[4] US FDA, Ctr Biol Evaluat & Res, Lab Parasit Biol & Biochem, Bethesda, MD USA
关键词
D O I
10.1128/AAC.45.12.3555-3559.2001
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
In this study, the in vitro and in vivo efficacies of free sodium stibogluconate (SSG) and a nonionic surfactant vesicular formulation of SSG (SSG-NIV) against a laboratory strain of Leishmania donovani (MHONVET/67: LV82) and different clinical isolates of L. donovani were determined. Treatment with SSG-NIV was more effective against intramacrophage amastigotes than treatment with SSG. In vivo murine studies showed that there was interstrain variability in the infectivity of the different L. donovani strains, with two of the strains (20001 and 20003) giving low parasite burdens. In addition, interstrain variability in the antileishmanial efficacy of SSG in a single dose containing 300 mg of Sb(V)/kg of body weight was observed. This dose of free drug either caused a > 97% reduction in liver parasite burdens or had no significant effect on parasite burdens compared with the result with the respective control. In some instances, treatment with this free SSG dose also caused a significant reduction in spleen (strain 20006) or bone marrow (strains 20001 and 20009) parasite burdens. Treatment with SSG-NIV was more effective than that with SSG against all of the strains tested. In SSG-responsive strains, the reduction in liver parasite burdens by SSG-NIV treatment was similar to that caused by free SSG. In SSG-nonresponsive strains, SSG-NIV treatment caused at least a 95% reduction in liver parasite burdens. Overall, these results indicate that the use of a vesicular formulation of SSG is likely to increase its clinical efficacy against visceral leishmaniasis.
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页码:3555 / 3559
页数:5
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