Tissue distribution of residual antimony in rats treated with multiple doses of meglumine antimoniate

摘要

Meglumine antimoniate (MA) and sodium stibogluconate are pentavalent antimony (SbV) drugs used since themid-1940s. Notwithstanding the fact that they are first-choice drugs for the treatment of leishmaniases, there aregaps in our knowledge of their toxicological profile, mode of action and kinetics. Little is known about the distributionof antimony in tissues after SbV administration. In this study, we evaluated the Sb content of tissues from malerats 24 h and three weeks after a 21-day course of treatment with MA (300 mg SbV/kg body wt/d, subcutaneous). Sbconcentrations in the blood and organs were determined by inductively coupled plasma-mass spectrometry. In rats,as with in humans, the Sb blood levels after MA dosing can be described by a two-compartment model with a fast (t1/2= 0.6 h) and a slow (t1/2 24 h) elimination phase. The spleen was the organ that accumulated the highest amountof Sb, while bone and thyroid ranked second in descending order of tissues according to Sb levels (spleen bone,thyroid, kidneys > liver, epididymis, lungs, adrenals > prostate > thymus, pancreas, heart, small intestines > skeletalmuscle, testes, stomach > brain). The pathophysiological consequences of Sb accumulation in the thyroid andSb speciation in the liver, thyroid, spleen and bone warrant further studies.