Mechanism of protective effect of fosfomycin against aminoglycoside ototoxicity.
The purpose of this study was to clarify the mechanism of the protective effect of fosfomycin (FOM) against inner ear damage induced by an aminoglycoside dibekacin (DKB), when administered concurrently DKB and FOM. Rats were treated with 50 mg/kg of DKB with or without 500 mg/kg of FOM for short-term administration. No significant difference was seen in the serum peak level and in the area under the curve between the group receiving DKB alone and the combined administration group of DKB and FOM. On the other hand, the DKB level in the kidney was significantly lower in the combined administration group than in the group receiving DKB alone. The mechanism of protective effect of FOM against DKB-induced ototoxicity may be considered as follows: FOM inhibits the accumulation of DKB in the kidney and reduces its concentration in the kidney and serum. Consequently, the transferability of DKB into the inner ear is decreased, and finally inner ear damage is reduced.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003982:Dibekacin / Q000097:blood / Q000633:toxicity*; D004334:Drug Administration Schedule; D007758:Ear, Inner / Q000187:drug effects*; D005578:Fosfomycin / Q000494:pharmacology*; D007612:Kanamycin / Q000031:analogs & derivatives*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344
D000900:Anti-Bacterial Agents; D005578:Fosfomycin; D003982:Dibekacin; D007612:Kanamycin