Delivery advantage to the unilateral kidney by direct drug application to the kidney surface in rats and pharmacokinetic verification based on a physiological model
Delivery advantage to the unilateral kidney by direct drug application to the kidney surface in rats and pharmacokinetic verification based on a physiological model
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DOI：
10.1080/10611860500159097
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发表时间：
2005-05
影响因子：
4.5
通讯作者：
K. Nishida;Manabu Kamenosono;A. Kuma;S. Fumoto;T. Mukai;M. Nakashima;H. Sasaki;J. Nakamura
中科院分区：
文献类型：
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作者：
K. Nishida;Manabu Kamenosono;A. Kuma;S. Fumoto;T. Mukai;M. Nakashima;H. Sasaki;J. Nakamura
本研究的目的是基于生理药代动力学模型，通过将药物直接应用于大鼠肾脏表面来评价单侧肾脏的药物递送优势。在麻醉下，将圆柱形扩散池（i.d. 6 mm，面积0.28 cm 2）附着于大鼠右肾表面。选择酚磺酞（PSP）作为模型化合物，加入扩散池中。以1 mg剂量应用于右肾表面后，右（应用）肾中的游离PSP浓度显著高于左（未应用）肾，直至应用后60 min。同样，从应用肾脏的尿中排泄率的游离PSP比从非应用肾脏快得多，与2.6倍以上的排泄量在240分钟。这些结果意味着一个相当大的药物输送优势，可以从肾脏表面直接吸收后，获得单侧肾脏的可能性。在0.3和1.5 mg的其他应用剂量下也观察到这种趋势。另一方面，异硫氰酸荧光素葡聚糖（Mw 4400，FD-4）从每个肾脏同等地排泄到尿液中，并且应用和未应用肾脏中的肾脏浓度几乎相同，这可能是由于吸收的FD-4的被动转运（即肾小球过滤）的参与。在肾脏表面应用后，基于生理模型的血浆和每个肾脏中游离PSP浓度的计算机模拟与相应的实验数据一致。此外，通过与其他途径（如i. v.和i.a.）的比较，证实了PSP肾表面应用的递送优势。行政部门。
The objective of this study was to evaluate the drug delivery advantage to the unilateral kidney by direct drug application to the rat kidney surface based on a physiological pharmacokinetic model. Under anesthesia, a cylindrical diffusion cell (i.d. 6 mm, area 0.28 cm2) was attached to the right kidney surface in rats. Phenolsulfonphthalein (PSP), an organic anion chosen as a model compound, was added into the diffusion cell. The free PSP concentration in the right (applied) kidney after application to the right kidney surface at a dose of 1 mg was significantly higher than that of the left (non-applied) kidney until 60 min after application. Similarly, the urinary excretion rate of free PSP from the applied kidney was much faster than that from the non-applied kidney, with a 2.6 times larger excreted amount in 240 min. These results imply the possibility that a considerable drug delivery advantage to the unilateral kidney could be obtained after direct absorption from the kidney surface. This tendency was also observed at the other application doses of 0.3 and 1.5 mg. On the other hand, fluorescein isothiocyanate dextran (Mw 4400, FD-4) was equally excreted into the urine from each kidney and the renal concentrations in the applied and non-applied kidneys were almost the same, possibly due to the involvement of passive transport for the absorbed FD-4, i.e. glomerular filtration. The computer simulations of free PSP concentrations in the plasma and each kidney based on a physiological model after kidney surface application were consistent with the respective experimental data. Moreover, the delivery advantage of kidney surface application of PSP was verified by its comparison with other routes such as i.v. and i.a. administrations.