Pharmacokinetics and tissue distribution of antimony after multiple intramuscular administration in the hamster

The fate of pentavalent antimony [Sb v] in different tissues in the body after intramuscular administration is of great interest for the future study of Sb v therapy in different sitting. Pharmacokinetics and tissue distribution of antimony [Sb v] were studied in the hamster after daily dose of sodium stibogluconate equivalent to 120 mg kg -1 of Sb v, administered intramuscularly for two weeks. Liver, spleen, heart, kidney and skin tissues were isolated after blood collection at the specified time. Antimony was measured in these tissues after suitable treatment, ashing and processing, by flameless atomic absorption spectrophotometry. The concentrations of Sb v time profile in blood showed a linear rapid decline with elimination half life [t 1/2] of 1.7 h. The concentration of drug [micro g/gm] declined in a biphasic manner from almost all tissues. However, the concentrations of Sb v were declined in slower fashion from the hamster tissues than from the blood. The maximum concentration of Sb v was determined in the kidney tissues [3416 +/- 631 micro g/gm] while the lowest concentration was in the spleen [209 +/- 187 micro g/gm]. The maximum concentration of Sb v in the kidney [micro g/gm] was more than 25 fold higher than that measured from blood [micro g/ml]. The AUC of Sb v in the studied tissues was in this rank: kidney> liver> skin> spleen > heart > blood. Surprisingly, the heart, spleen and liver showed a similar t 1/2 of 5.2-6.2 h while the kidney and skin had a t 1/2 of about 3 h. Therefore, disposition of Sb v seems to kinetically follow multicompartmental model. The kidneys got the highest concentration of drug which may lead to nephrotoxicity on long term therapy

efficacy of different dosage regimens of pentavalent antimony on cutaneous leishmaniasis in mice

The efficacy of different dosage regimens of sodium stibogluconate [SSG], a pentavalent antimony [sb] agent in the treatment of cutaneous leishmaniasis [CL] in male Balb/c mice was investigated. Mice with CL were divided into four groups. Mice in group 1, were injected intramuscularly with saline [control] and those in groups 2, 3 and 4 were injected with a total daily dose of 300 mg Sb/kg :300 once 150 twice and 100 thrice mg sb/kg respectively daily for 10 days. None of the mice in groups 1 or 4 was cured, however the cure rates in groups 2 and 3 were 50% and 33%, respectively. Lesion size was reduced by 89% in group 2 as compared to 56% and 16% in groups 3 and 4 respectively. Peak plasma antimony level [C[max]]was determined in another 3 groups of mice that were given 300, 150 and 100 mg sb/kg. The C[max] were: 34.3, 15.9 and 8.4 micro g /ml in groups 1.2 and 3 respectively. Those of groups 1 and 2 but not 3 were within the in vitro ED50 range [12-20 mg/1] of SSG. In conclusion, higher cure and healing rates as well as a more effective antimony plasma level are obtained when the total daily requirements of SSG is given as a single dose. This regimen should, thus be used instead of divided doses when treating CL