Beck H, Züllich B, Marre R, Sack K
Arzneimittelforschung. 1979;29(6):935-9.
In studies on female Wistar rats (n = 133) the nephrotoxicity and kidney concentrations of amikacin, butirosin, gentamicin, kanamycin, bekanamycin, sisomicin, and tobramycin were examined during four weeks therapy and four weeks convalescence. Maximum doses recommended for human therapy were administered i.m. at 12-h intervals. For evaulation of the tubulotoxic effect the excretion rates of tubular cells were determined daily. At weekly intervals animals were sacrificed for determination of the kidney aminoglycoside concentration, which was assayed microbiologically. The application of all aminoglycosides resulted in an increase of excreted tubular cells, but the extent and course of cell excretion varied for the different aminoglycosides. An initial peak after different periods of therapy and later on a decrease of cell excretion was found for all aminoglycosides. These periods of high and low loss of tubular cells corresponded to aminoglycoside accumulation and saturation in the kidneys. During the first week of treatment only gentamicin was tolerated without signs of renal damage. Initially the nephrotoxic effect was strongest for bekanamycin, but at the end of the first week kanamycin and sisomicin produced similar distinct side effects. Thereafter the highest cell excretion rates were continuously caused by sisomicin.
