Gutiérrez Millán Carmen, Zarzuelo Castañeda Aránzazu, González López Francisco, Sayalero Marinero María Luisa, Lanao José M
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Salamanca, Salamanca, Spain.
J Antimicrob Chemother. 2008 Feb;61(2):375-81. doi: 10.1093/jac/dkm477. Epub 2007 Dec 19.
To study the changes in the pharmacokinetics and tissue distribution of the aminoglycoside amikacin in rats using amikacin carrier erythrocytes as a delivery system.
Amikacin-loaded erythrocytes were obtained using a hypotonic dialysis method. The pharmacokinetic and tissue distribution of amikacin were studied in three groups of rats receiving intravenous amikacin in saline solution, amikacin-loaded erythrocytes and amikacin-loaded erythrocytes treated with glutaraldehyde. Pharmacokinetic analysis was accomplished using model-independent methods.
Administration of the antibiotic using carrier erythrocytes elicited a sustained release effect, with an increase in the plasma half-life and in the area under the curve of the antibiotic. The tissue pharmacokinetics of amikacin using carrier erythrocytes in comparison with a control group revealed an accumulation of the antibiotic in specific tissues such as the liver and spleen, a similar pharmacokinetics in the lung and moderate changes in the pharmacokinetics in the kidney. Studies of tissue concentrations after the injection of glutaraldehyde-treated loaded erythrocytes demonstrated important changes in organs of the reticulo-endothelial system (RES) in comparison with the results observed for standard carrier erythrocytes, higher levels being observed in the liver whereas spleen levels decreased.
The administration of amikacin in loaded erythrocytes in rats leads to significant changes in the pharmacokinetic behaviour of the antibiotic, a greater accumulation being observed in RES organs such as liver and spleen. This shows that loaded erythrocytes are potentially useful for the delivery of antibiotics in phagocytic cells located in the RES.
以阿米卡星载体红细胞作为递送系统，研究氨基糖苷类药物阿米卡星在大鼠体内的药代动力学和组织分布变化。
采用低渗透析法制备负载阿米卡星的红细胞。在三组大鼠中研究阿米卡星的药代动力学和组织分布，这三组大鼠分别接受静脉注射生理盐水溶液中的阿米卡星、负载阿米卡星的红细胞以及经戊二醛处理的负载阿米卡星的红细胞。使用非模型依赖方法进行药代动力学分析。
使用载体红细胞给药抗生素产生了缓释效果，抗生素的血浆半衰期和曲线下面积增加。与对照组相比，使用载体红细胞的阿米卡星组织药代动力学显示抗生素在肝脏和脾脏等特定组织中蓄积，在肺部药代动力学相似，在肾脏中药代动力学有适度变化。注射经戊二醛处理的负载红细胞后组织浓度的研究表明，与标准载体红细胞观察到的结果相比，网状内皮系统（RES）器官有重要变化，肝脏中观察到更高水平，而脾脏水平下降。
在大鼠中用负载红细胞给药阿米卡星会导致抗生素药代动力学行为发生显著变化，在肝脏和脾脏等RES器官中观察到更大的蓄积。这表明负载红细胞对于在RES中的吞噬细胞中递送抗生素可能是有用的。
