Chauvin J M, Rudhardt M, Blanchard P, Gaillard R, Fabre J
Schweiz Med Wochenschr. 1978 Jul 8;108(27):1020-5.
The injection in rats of 4 mg/kg gentamicin results in accumulation and continued presence of the antibiotic in the renal parenchyma compared with its rapid elimination from other tissues. With repeated injections at 24-hour intervals over a period of 3 weeks, gentamicin concentrations in the cortex reach 356 +/- 139 microgram/g after 1 week of treatment, i.e. levels 50 times higher than the maximum serum levels. They then stay at a saturation plateau before decreasing very slowly to levels of 50 microgram/g 2 weeks and 15 microgram/g 15 weeks after the last injection. The accumulation takes place mainly in the cells of the proximal convoluted tubule. In the medulla, gentamicin behaves similarly but the levels are lower. Weeks after the last injection, urine levels of gentamicin are still appreciable. In spite of this enormous accumulation, the treatment does not result in disturbance of renal function or striking morphological changes. These observations are based on dosages of gentamicin corresponding to those used clinically. Compared to earlier observations based on the supratherapeutic administration of the antibiotic, the present study provides a better understanding of the mechanisms involved in gentamicin nephrotoxicity.
给大鼠注射4mg/kg庆大霉素后，抗生素会在肾实质中蓄积并持续存在，而在其他组织中则会迅速消除。在3周的时间里，每隔24小时重复注射一次，治疗1周后，皮质中的庆大霉素浓度达到356±139微克/克，即比血清最高水平高50倍。然后它们会保持在饱和平台期，之后非常缓慢地下降，在最后一次注射后2周降至50微克/克，15周后降至15微克/克。蓄积主要发生在近端曲管的细胞中。在髓质中，庆大霉素的行为类似，但水平较低。最后一次注射数周后，庆大霉素的尿液水平仍然可观。尽管有如此大量的蓄积，但治疗并未导致肾功能紊乱或明显的形态学变化。这些观察结果基于与临床使用剂量相当的庆大霉素剂量。与早期基于超治疗剂量抗生素给药的观察结果相比，本研究对庆大霉素肾毒性的相关机制有了更好的理解。
