The influence of Fosfomycin (FOM) on inner ear and renal damage due to Dibekacin(DKB) was investigated using Fischer 344 rats as the experimental animals. DKB (100mg/kg/dayor 50mg/kg/day) was administered in single daily either alone or in combination with 500mg/kg/day of FOM for 60 or 120 consecutive days. Four hours after the last injection the animalswere decapitated and the DKB levels of serum, kidney and perilymph were measured by the bioassay method. Using the surface preparation technique the hair cell damage of the inner ear was examined by means of a phase contrast microscope. The renal damage was examined with a light microscope. Renal function parameters, BUN, urinary NAG activity and urinary protein, were measured. DKB levels of the serum and kidneys were also observed after the first and fifth injection of DKB (50mg/kg) alone and in combination with FOM (500mg/kg).
The results were as follows. 1. The hair cell damage and renal damage including both histological and functional damage due to DKB were reduced by combined administration with FOM. 2. When administered in combination with FOM, the DKB levels of the serum, kidneys and perilymph after 60 or 120 injections were lower than when DKB was administered alone. 3. After the first and fifth injection the serum DKB levels were not significantly different between the two groups but the kidney DKB levels after the fifth injection were lower in the animals receiving FOM, although the accumulation of DKB was observed in both groups.
It is thought that the protective effect of FOM against DKB induced ototoxicity is related to the concentration of DKB in the kidneys, serum and perilymph. The decrease of the concentration of DKB was attributed to FOM's inhibition of the accumulation of DKB in the kidneys and not to the acceleration of DKB excretion from the kidneys by FOM.
It is concluded that this combined administration first inhibits the accumulation of DKB in the kidneys and then decreases the serum and perilymph DKB levels, resulting in a subsequent reduction in inner ear damage.
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