Comparative Ototoxicity of Ribostamycin, Dactimicin, Dibekacin, Kanamycin, Amikacin, Tobramycin, Gentamicin, Sisomicin and Netilmicin in the Inner Ear of Guinea Pigs

Abstract

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 > GM > TOB > AMK > DKB > KM > NTL, DAC RSM, whereas the vestibular toxicity was in the following order: SISO > GM > DKB > TOB > NTL > AMK > KM > 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.

Phospholipon 90H (P90H)–based PEGylated microscopic lipospheres delivery system for gentamicin: an antibiotic evaluation

“…Currently, effective bacteriocidal therapy using gentamicin hinges upon either intravenous infusion or intramuscular administration [16] . Parenteral administration of gentamicin has been associated with side effects that include mainly nephrotoxicity and ototoxicity [17][18][19] .…”

A new immunohistochemical method for the detection of gentamicin in inner ear fluid compartments

“…T h e uptake o f G M in inner ear tissues is rapid, in contrast to its s l o w e l i m i n a t i o n [22]. G M is also the a m i n o g l y c o s i d e antibiotic w i t h the h i g h e s t ototoxic potential [16]. This is due to the cationic character o f the m o l e c u l e u n d e r p h y s i o l o g i c a l p H conditions.…”

“…Pharmacokinetic studies have revealed that aminoglycoside antibiotics are slowly eliminated [7,16,20] and accumulate in the inner ear, especially in the outer hair cells [8,9,14], Deiter's and Hensen's cells and the stria vascularis [10], as well as in type I cells of the vestibule [13]. Although the concentration of aminoglycoside antibiotics in the peri-and endolymph can be correlated with that in the plasma, the level in plasma is much higher than in inner ear fluids [21].…”

“…This is due to the cationic character o f the m o l e c u l e u n d e r p h y s i o l o g i c a l p H conditions. Furthermore, a correlation exists b e t w e e n the n u m b e r o f a m i n o groups and the o t o t o x i c side effects p r o d u c e d [16]. …”

Development of a monoclonal antibody assay and immunochromatographic test strip for the detection of amikacin residues in milk and eggs

“…When used in the treatment of cow mastitis, adequate withdrawal periods are required to avoid the occurrence of amikacin residues in the milk (Chen et al, 2012). This is important because amikacin has earlier been reported to have potential ototoxicity (Kitasato, Yokota, Inouye, & Igarashi, 2004;Zawilla et al, 2007) and nephrotoxicity (Luft et al, 1978;Serrano & Silva, 2006).…”