Auditory function in guinea pigs treated with netilmicin and other aminoglycoside antibiotics

Abstract

The following aminoglycoside antibiotics netilmicin, sisomicin, gentamicin, and kanamycin were submitted to a comparative study of their ototoxicity using both reflexological (Preyer's pinnareflex) and electrophysiological (near and far field) methods. The daily s.c. administration of sisomicin, gentamicin, and kanamycin for 21 days provoked a dose-related impairment of the cochlear function, detected with all the employed techniques. On the other hand, a very low ototoxic effect of netilmicin was demonstrated with electrophysiological but not with the reflexological evaluation. The reliability of the methods used in these experiments is also compared.

Comparative Ototoxicity of Dibekacin and Netilmicin in Guinea Pigs

“…The present study demonstrated that the vestibular and cochlear reflexes and electrophysiologic responses in guinea pigs dosed with netilmicin at 150 mg/kg/day for 21 days, were similar to those of saline-injected. These results confirm previous observations on the safety of netilmicin on the inner ear of guinea pigs (Brummett et al 1978;Arpini et al 1979;Bamonte et al 1980;Wersall 1980), cats (Weinberg et al 1981), monkeys (Igarashi et al 198 1) dogs and rats (Igarashi & Jensen 1981).…”

“…1980) and less ototoxic (Brummett et a/. 1978;Arpini et a/. 1979;Bamonte et al 1980;Wersall 1980) than the other currently available aminoglycosides.…”

Comparative pharmacokinetics of aminoglycoside antibiotics in guinea pigs

“…The disposition half-lives (t11n) in plasma of the three antibiotics were comparable and within the following ranges: tl/,2a of 0.09 to 0.16 h; tl2p of 0.88 to 1.01 h; and t1/2y of 7.87 to 8.29 h. The volume of distribution in the central compartment and the total body clearance of netilmicin (294 mI/kg, 5.74 ml/min per kg) were greater than those of gentamicin (160 ml/kg, 3.40 m/min per kg) and tobramycin (204 ml/kg, 4.63 ml/min per kg). Pharmacokinetic analysis of the perilymph drug concentration-time data indicated that all three antibiotics penetrated the perilymph readily, but netilmicin cleared from the perilymph compartment faster than gentamicin and tobramycin.…”

“…It has been reported that the aminoglycoside antibiotics that are widely used in clinical practice, such as gentamicin, tobramycin, and amikacin, show similar perilymph drug concentrations (5) and provoke substantially overlapping ototoxic reactions (1,3,5,9). Studies on neomycin, streptomycin, dihydrostreptomycin, and kanamycin (8,11) also have shown that the relative ability of each aminoglycoside antibiotic to reach greater perilymph concentration was directly related to the extent of their ototoxic damage in guinea pigs.…”

Comparative uptake of gentamicin, netilmicin, and amikacin in the guinea pig cochlea and vestibule

“…The morphological changes and electrophysiological dysfunctions induced by different aminoglycosides have been extensively studied, and it is clearly established that the pattern of toxicity varies greatly within this family of antibiotics (1,8,12). For example, gentamicin affects the cochlear and vestibular systems to nearly the same extent, while amikacin preferentially damages the cochlea; netilmicin is significantly less toxic than either gentamicin or amikacin to both parts of the labyrinth (2,5,7). It has been postulated that this differential damage is related to the concentration of aminoglycoside achieved in the perilymph, i.e., the more toxic a drug, the higher its level in this inner-ear fluid (7,20), although exceptions from this pattern had been noted (6,15).…”