Xavier Holanda C M C, Cavalcanti Jales R L, Almeida Catanho M T J, Holanda Leite R C, Lopes de Brito L M, Jales-Junior L H, Brandao K C, Amorim L F, de Brito Tiago G G, Gomes M L, Bernardo-Filho M
Universidade Federal do Rio Grande do Norte, Centro de Biociências, Departamento de Microbiologia e Parasitologia, Av. Salgado Filho, 3000, 59078-970, Natal, RN, Brazil.
Cell Mol Biol (Noisy-le-grand). 2002 Nov;48(7):761-5.
There are evidences that some drugs used for the human diseases can modify the biodistribution of radiopharmaceuticals. The N-methyl meglumine antimoniate, commercially known as glucantime (Rhodia, Brazil), is the elected drug for the treatment of all the clinical forms of leishmaniasis. As therapeutic drugs can present important toxic effects, we studied the effects of the glucantime on the kinetic of biodistribution of radiopharmaceuticals. To study the glucantime effect on the biodistribution of technetium-99m-methylenediphosphonic acid (99mTc-MDP), glucantime IM (80 mg/kg/day) was administered into male Wistar rats (3 months old age) in single dose during 7 days. 99mTc-MDP was injected 1 hr after the last dose. The animals (n = 24) were divided into two groups: treated (n = 12) and control (n = 12) and they were rapidly sacrificed, respectively, in 3 periods (5, 30 and 120 min) after administration of the 99mTc-MDP. The organs were isolated (brain, heart, thyroid, lungs, kidneys, testis, stomach, intestines, pancreas, spleen, liver, muscle, bone and bladder) and the percentages of radioactivity (%ATI) in each organ were calculated. The results were analyzed by the Wilcoxon test (p < 0.05). The analysis of the results has shown a significant increase of the %ATI after 5 min administration of the 99mTc-MDP in spleen, kidneys, testis, heart, liver and a reduction of %ATI in bladder. Thirty minutes after administration of the 99mTc-MDP, the analysis ofthe results reveals a significant reduction of the %ATI in femur, kidneys, thin bowel, lungs, heart, liver and an increase in abdominal muscle and stout bowel. One hundred-twenty min after administration of the 99mTc-MDP, the analysis of the results shows a significant reduction of the %ATI in spleen, thyroid, blood, femur, kidneys, liver and an increase in bladder, pancreas and lungs. Biochemical dosages were also performed before (control group, n = 12) and after (treated group, n = 12) treatment with glucantime. There was a significant (p < 0.05) decrease to the biochemical levels after the treatment with glucantime in following dosages: blood urea nitrogen, creatinine, alkaline phosphatase, lactic dehydrogenase, aspartate amino transferase, total creatine kinase, total protein, globulin and albumin. These results were compared with the control group, without glucantime, and statistical analyses were performed (t-student test, p < 0.05). These results could be associated with the biological effects and/or metabolization of the studied drug.
有证据表明,一些用于治疗人类疾病的药物可改变放射性药物的生物分布。N-甲基葡甲胺锑酸盐,商品名为葡糖胺锑(巴西罗地亚公司生产),是治疗所有临床类型利什曼病的首选药物。由于治疗药物可能会产生重要的毒性作用,我们研究了葡糖胺锑对放射性药物生物分布动力学的影响。为研究葡糖胺锑对锝-99m-亚甲基二膦酸(99mTc-MDP)生物分布的影响,对雄性Wistar大鼠(3月龄)单剂量注射葡糖胺锑IM(80mg/kg/天),持续7天。在最后一剂后1小时注射99mTc-MDP。将动物(n = 24)分为两组:治疗组(n = 12)和对照组(n = 12),在注射99mTc-MDP后的3个时间段(5、30和120分钟)分别迅速处死。分离出各器官(脑、心、甲状腺、肺、肾、睾丸、胃、肠、胰腺、脾、肝、肌肉、骨和膀胱),计算每个器官的放射性百分比(%ATI)。结果采用Wilcoxon检验进行分析(p < 0.05)。结果分析显示,注射99mTc-MDP 5分钟后,脾、肾、睾丸、心、肝的%ATI显著增加,膀胱的%ATI降低。注射99mTc-MDP 30分钟后,结果分析显示股骨、肾、小肠、肺、心、肝的%ATI显著降低,腹肌和大肠的%ATI增加。注射99mTc-MDP 120分钟后,结果分析显示脾、甲状腺、血液、股骨、肾、肝的%ATI显著降低,膀胱、胰腺和肺的%ATI增加。在使用葡糖胺锑治疗前(对照组,n = 12)和治疗后(治疗组,n = 12)还进行了生化检测。葡糖胺锑治疗后,以下生化指标水平显著降低(p < 0.05):血尿素氮、肌酐、碱性磷酸酶、乳酸脱氢酶、天冬氨酸氨基转移酶、总肌酸激酶、总蛋白、球蛋白和白蛋白。将这些结果与未使用葡糖胺锑的对照组进行比较,并进行统计分析(t检验,p < 0.05)。这些结果可能与所研究药物的生物学效应和/或代谢有关。