Investigations on the potential nephrotoxicity of cefazedone and gentamicin and of their combination, in comparison with the combination of cefazolin and cephalothin with gentamicin.

The nephrotoxicity of (6R,7R)-7-(2-[3,5-Dichloro-4-oxo-1(4H)-pyridyl]-acetamido)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)-thio]methyl)-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid (cefazedone, Refosporen), cephalothin, cefazolin and gentamicin was investigated by the determination of alanine-amino-peptidase (AAP) in urine of healthy volunteers. The results were compared with those obtained by application of the respective combination. The beta-lactam antibiotics showed no effect on the elimination of the characteristic tubule enzyme, while gentamicin, as is known, induced a marked increase of the enzyme elimination. The results with cefazedone + gentamicin show that the determining component on the extent of AAP elimination is the aminoglycoside exclusively, where high and low responders can be observed. When the experiments with gentamicin and with the combination gentamicin and cefazedone were carried out with the same volunteers, no additive effects could be observed.