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Antimicrobial Agents and Chemotherapy, December 2001, p. 3555-3559, Vol. 45, No. 12
Departments of
Immunology1 and Pharmaceutical
Sciences,2 University of Strathclyde,
Glasgow, United Kingdom; Institute of Medical Sciences, Banaras Hindu
University, Varanasi, India3; and
Laboratory of Parasitic Biology and Biochemistry, Center
for Biologics Evaluation and Research, Food and Drug
Administration, Bethesda, Maryland4
Received 9 May 2001/Returned for modification 18 June 2001/Accepted 13 September 2001
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 (MHOM/ET/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.
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.12.3555-3559.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Efficacies of Vesicular and Free Sodium
Stibogluconate Formulations against Clinical Isolates of
Leishmania donovani
*
Corresponding author. Mailing address: Department of
Immunology, SIBS Building, 31 Taylor St., University of Strathclyde, Glasgow G4 ONR, United Kingdom. Phone: 0141-548-3823 or 0141-548-3531. Fax: 0141-548-3427. E-mail: k.carter{at}strath.ac.uk.
Antimicrobial Agents and Chemotherapy, December 2001, p. 3555-3559, Vol. 45, No. 12
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.12.3555-3559.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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