Comparative ototoxicity of ribostamycin, dactimicin, dibekacin, kanamycin, amikacin, tobramycin, gentamicin, sisomicin and netilmicin in the inner ear of guinea pigs.
Nine aminoglycoside antibiotics, ribostamycin (RSM), dactimicin (DAC), dibekacin (DKB), kanamycin (KM), amikacin (AMK), netilmicin (NTL), tobramycin (TOB), gentamicin (GM) and sisomicin (SISO) were administered intramuscularly to guinea pigs for 4 weeks, and ototoxicity and drug concentration in the inner ear fluid were determined. RSM and DAC showed the weakest ototoxicity against the cochlea and vestibular organs. AMK and KM were more toxic to cochlea than vestibular organs. DKB, TOM, GM and SISO were equally toxic to vestibular organs and cochlea. NTL was more toxic to vestibular organs than cochlea. As judged from the pinna reflex response and hair cell damage in the cochlea, the order of auditory toxicity was the following: SISO greater than GM greater than TOB greater than AMK greater than DKB greater than KM greater than NTL, DAC RSM, whereas the vestibular toxicity was in the following order: SISO greater than GM greater than DKB greater than TOB greater than NTL greater than AMK greater than KM greater than DAC, RSM. RSM, causing the weakest ototoxicity, showed a low drug concentration in the inner ear fluid, while GM, causing severe ototoxicity, showed the highest drug level under the same conditions.
Kitasato
I
I
Research and Development, Meiji Seika Kaisha, Ltd., Tokyo, Japan.
Yokota
M
M
Inouye
S
S
Igarashi
M
M
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects; D007758:Ear, Inner / Q000187:drug effects*; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects; D007273:Injections, Intramuscular; D008297:Male; D010498:Perilymph / Q000032:analysis; D012021:Reflex, Abnormal / Q000187:drug effects; D013997:Time Factors
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents