Ciprofloxacin and the inner ear--a morphological and round window membrane permeability study.
This study was conducted in order to evaluate ototoxic potential and passage through the round window membrane of ciprofloxacin, a newly developed antimicrobial drug with an antibacterial spectrum well suited for the treatment of suppurative otitis media. Ciprofloxacin was injected intraperitoneally in 40 guinea pigs in doses ranging from 25 to 150 mg/kg body weight for 14 consecutive days. Sixteen inner ears of chinchillas were exposed to ciprofloxacin at a concentration of 0.1 mg/ml applied directly to the intact round window membrane. Despite severe deterioration of the animals injected with the highest doses, no behavioral or definite morphological evidence of inner ear or vestibular damage could be seen. Ciprofloxacin concentrations in the perilymph were determined with high-performance liquid chromatography. Direct passage of ciprofloxacin, presumably via the round window membrane, was demonstrated. After 1 h and 15 min, an arithmetic mean concentration of 0.165 micrograms/ml (95% confidence interval +/- 0.053) could be demonstrated in the perilymph. It can be concluded that ciprofloxacin has no ototoxic effect when administered systemically. Furthermore, when locally applied into the middle ear, it has the capacity to pass into the inner ear.
Bagger-Sjöbäck
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Department of Otolaryngology, Karolinska Institute, Karolinska Hosital, Stockholm, Sweden.
Lundman
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Nilsson-Ehle
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D000818:Animals; D002682:Chinchilla; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D007758:Ear, Inner / Q000187:drug effects* / Q000648:ultrastructure; D004432:Ear, Middle; D006168:Guinea Pigs; D008855:Microscopy, Electron, Scanning; D009925:Organ of Corti / Q000187:drug effects / Q000648:ultrastructure; D010498:Perilymph / Q000737:chemistry; D010539:Permeability; D012405:Round Window, Ear / Q000378:metabolism*; D014722:Vestibule, Labyrinth / Q000187:drug effects
D002939:Ciprofloxacin