Borborema Samanta Etel Treiger, Osso João Alberto, de Andrade Heitor Franco, do Nascimento Nanci
Center for Biotechnology, Nuclear and Energy Research Institute, São Paulo, SP, Brazil.
Center for Parasitology and Mycology, Adolfo Lutz Institute, São Paulo, SP, Brazil.
J Venom Anim Toxins Incl Trop Dis. 2019 Mar 11;25:e144618. doi: 10.1590/1678-9199-JVATITD-1446-18. eCollection 2019.
Cutaneous leishmaniasis (CL) is a parasitic disease caused by the protozoan spp. Pentavalent antimonial agents have been used as an effective therapy, despite their side effects and resistant cases. Their pharmacokinetics remain largely unexplored. This study aimed to investigate the pharmacokinetic profile of meglumine antimoniate in a murine model of cutaneous leishmaniasis using a radiotracer approach.
Meglumine antimoniate was neutron-irradiated inside a nuclear reactor and was administered once intraperitoneally to uninfected and . -infected BALB/c mice. Different organs and tissues were collected and the total antimony was measured.
Higher antimony levels were found in infected than uninfected footpad (0.29% IA vs. 0.14% IA, p = 0.0057) and maintained the concentration. The animals accumulated and retained antimony in the liver, which cleared slowly. The kidney and intestinal uptake data support the hypothesis that antimony has two elimination pathways, first through renal excretion, followed by biliary excretion. Both processes demonstrated a biphasic elimination profile classified as fast and slow. In the blood, antimony followed a biexponential open model. Infected mice showed a lower maximum concentration (6.2% IA/mL vs. 11.8% IA/mL, p = 0.0001), a 2.5-fold smaller area under the curve, a 2.7-fold reduction in the mean residence time, and a 2.5-fold higher clearance rate when compared to the uninfected mice.
neutron-irradiated meglumine antimoniate concentrates in infected footpad, while the infection affects antimony pharmacokinetics.
皮肤利什曼病（CL）是由原生动物利什曼原虫属物种引起的一种寄生虫病。尽管五价锑剂存在副作用和耐药病例，但一直被用作有效的治疗药物。其药代动力学在很大程度上仍未得到充分研究。本研究旨在使用放射性示踪剂方法，在皮肤利什曼病小鼠模型中研究葡甲胺锑酸盐的药代动力学特征。
葡甲胺锑酸盐在核反应堆内进行中子辐照，然后对未感染和感染利什曼原虫的BALB/c小鼠进行一次腹腔注射。收集不同的器官和组织并测量总锑含量。
在感染的足垫中发现锑水平高于未感染的足垫（0.29%注入量对0.14%注入量，p = 0.0057），且该浓度得以维持。动物在肝脏中积累并保留锑，清除缓慢。肾脏和肠道摄取数据支持以下假设：锑有两条消除途径，首先是通过肾脏排泄，其次是通过胆汁排泄。这两个过程均表现出分为快速和缓慢的双相消除特征。在血液中，锑遵循双指数开放模型。与未感染的小鼠相比，感染的小鼠显示出较低的最大浓度（6.2%注入量/毫升对11.8%注入量/毫升，p = 0.0001）、曲线下面积小2.5倍、平均驻留时间减少了2.7倍以及清除率高2.5倍。
经中子辐照的葡甲胺锑酸盐集中在感染的足垫中,而感染会影响锑的药代动力学。
