Schettini D A, Costa Val A P, Souza L F, Demicheli C, Rocha O G F, Melo M N, Michalick M S M, Frézard F
Departamentos de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
Braz J Med Biol Res. 2003 Feb;36(2):269-72. doi: 10.1590/s0100-879x2003000200015. Epub 2003 Jan 29.
The achievement of complete cure in dogs with visceral leishmaniasis is currently a great challenge, since dogs are the main reservoir for the transmission of visceral leishmaniasis to humans and they respond poorly to conventional treatment with pentavalent antimonials. In order to improve the efficacy of treatment, we developed a novel formulation for meglumine antimoniate based on the encapsulation of this drug in freeze-dried liposomes (LMA). The aim of the present study was to evaluate the biodistribution of antimony (Sb) in dogs following a single intravenous bolus injection of LMA. Four healthy male mongrel dogs received LMA at 3.8 mg Sb/kg body weight and were sacrificed 3, 48 and 96 h and 7 days later. Antimony was determined in the blood, liver, spleen and bone marrow. In the bone marrow, the highest Sb concentration was observed at 3 h (2.8 microg/g wet weight) whereas in the liver and spleen it was demonstrated at 48 h (43.6 and 102.4 microg/g, respectively). In these organs, Sb concentrations decreased gradually and reached levels of 19.1 microg/g (liver), 28.1 microg/g (spleen) and 0.2 microg/g (bone marrow) after 7 days. Our data suggest that the critical organ for the treatment with LMA could be the bone marrow, since it has low Sb levels and, presumably, high rates of Sb elimination. A multiple dose treatment with LMA seems to be necessary for complete elimination of parasites from bone marrow in dogs with visceral leishmaniasis.
目前，实现内脏利什曼病犬的完全治愈是一项巨大挑战，因为犬是内脏利什曼病向人类传播的主要储存宿主，且它们对传统的五价锑治疗反应不佳。为了提高治疗效果，我们开发了一种基于将葡甲胺锑酸盐包裹于冻干脂质体（LMA）中的新型制剂。本研究的目的是评估单次静脉推注LMA后犬体内锑（Sb）的生物分布。4只健康雄性杂种犬接受了3.8mg Sb/kg体重的LMA，并分别在3、48、96小时及7天后处死。对血液、肝脏、脾脏和骨髓中的锑进行了测定。在骨髓中，3小时时观察到最高的Sb浓度（2.8μg/g湿重），而在肝脏和脾脏中，48小时时出现最高浓度（分别为43.6和102.4μg/g）。在这些器官中，Sb浓度逐渐降低，7天后分别降至19.1μg/g（肝脏）、28.1μg/g（脾脏）和0.2μg/g（骨髓）。我们的数据表明，LMA治疗的关键器官可能是骨髓，因为其Sb水平较低，且推测Sb清除率较高。对于内脏利什曼病犬，似乎需要多次给予LMA治疗才能从骨髓中完全清除寄生虫。
