De Broe M E, Paulus G J, Verpooten G A, Roels F, Buyssens N, Wedeen R, Van Hoof F, Tulkens P M
Kidney Int. 1984 Apr;25(4):643-52. doi: 10.1038/ki.1984.69.
The early alterations at the level of the proximal tubule of the human kidney caused by the three most currently used aminoglycosides, gentamicin, tobramycin, and amikacin, were studied. A prospective, randomized, and comparative approach using multidisciplinary methods was used. The patients received either no treatment or one of the three aminoglycosides at a therapeutic dose for 4 days preceding nephrectomy for neoplasia partly involving one kidney. The three aminoglycosides studied induce an early lysosomal phospholipidosis. Gentamicin and tobramycin cannot be distinguished on the basis of drug tissue accumulation, lysosomal overloading, or effect on lysosomal phospholipase A1. Amikacin induces significantly lower lysosomal overloading and no loss of phospholipase A1 activity.
研究了目前最常用的三种氨基糖苷类药物庆大霉素、妥布霉素和阿米卡星对人肾近端小管水平的早期改变。采用了一种前瞻性、随机且具有多学科方法的比较研究方法。在因肿瘤部分累及一侧肾脏而进行肾切除术之前,患者接受4天的无治疗或三种氨基糖苷类药物之一的治疗剂量。所研究的三种氨基糖苷类药物均会引发早期溶酶体磷脂沉积症。基于药物组织蓄积、溶酶体过载或对溶酶体磷脂酶A1的影响,无法区分庆大霉素和妥布霉素。阿米卡星引发的溶酶体过载显著较低,且磷脂酶A1活性未丧失。