Kikuchi S, Aramaki Y, Nonaka H, Tsuchiya S
Tokyo College of Pharmacy, Japan.
Pharm Res. 1990 Jun;7(6):644-7. doi: 10.1023/a:1015830614244.
The effect of dextran sulfate of three molecular weights (1000, 5000, and 90,000) on the accumulation of gentamicin in rat kidney was investigated using a continuous infusion technique. During the infusions of both gentamicin and gentamicin-dextran sulfate mixtures, the gentamicin plasma concentration was maintained at 10 microgram/ml. The renal cortical accumulation of gentamicin was significantly lower when dextran sulfate (1000, 5000) was coadministered. The inhibition of cortical gentamicin accumulation increased with increasing dextran sulfate dose, and it was proportional to the amount of dextran sulfate excreted into the urine. Analysis by electrophoresis on cellulose acetate membrane indicated that gentamicin binds to dextran sulfate in rat urine. Therefore, gentamicin-dextran sulfate binding within the lumen of the proximal tubules may reduce the renal reabsorption and possibly the renal toxicity of gentamicin.
采用连续输注技术研究了三种分子量（1000、5000和90000）的硫酸葡聚糖对庆大霉素在大鼠肾脏中蓄积的影响。在输注庆大霉素和庆大霉素 - 硫酸葡聚糖混合物的过程中，庆大霉素血浆浓度维持在10微克/毫升。当联合给予硫酸葡聚糖（1000、5000）时，庆大霉素在肾皮质的蓄积显著降低。皮质庆大霉素蓄积的抑制作用随硫酸葡聚糖剂量的增加而增强，且与排泄到尿液中的硫酸葡聚糖量成正比。醋酸纤维素膜电泳分析表明，庆大霉素在大鼠尿液中与硫酸葡聚糖结合。因此，近端小管腔内的庆大霉素 - 硫酸葡聚糖结合可能会减少庆大霉素的肾重吸收，并可能降低其肾毒性。
