VISCERAL LEISHMANIASIS IN THE BALB C MOUSE - SODIUM STIBOGLUCONATE TREATMENT DURING ACUTE AND CHRONIC STAGES OF INFECTION .2. CHANGES IN TISSUE DRUG DISTRIBUTION

Animals with either an acute or chronic Leishmania donovani infection were treated with free or vesicular sodium stibogluconate (SSG) and tissue antimony levels and parasite suppressions in spleen, liver and bone marrow (femur) sites assessed. Treatment with free or vesicular SSG caused a significant suppression in spleen (p < 0.01) and liver (p < 0.001) parasite numbers compared to control values in the acute model. In the chronic model, treatment with free SSG was ineffective against spleen, liver and bone marrow parasites (similar burdens present in control and free drug treated animals) and vesicular SSG only significantly suppressed liver (p < 0.005) parasite burdens compared with controls. Dosing with free SSG resulted in higher mean tissue antimony concentrations in the liver, spleen, femur and kidney of acute infection mice compared to those obtained in chronic infection animals, however these differences were only statistically significant in the spleen (p < 0.05). If the marked hepatosplenomegaly caused by L. donovani infection is taken into account then the total amount of antimony present in the liver and spleen after free drug dosing was similar in acute and chronic infection mice. Administration of vesicular SSG to the two groups of mice resulted in higher antimony concentrations and higher total antimony levels in the spleen and liver compared with those achieved by free drug treatment (p < 0.05). The implications of the results are discussed.