Christensen E F, Reiffenstein J C, Madissoo H
Antimicrob Agents Chemother. 1977 Aug;12(2):178-84. doi: 10.1128/AAC.12.2.178.
The ototoxic potentials of two aminoglycoside antibiotics, amikacin and gentamicin, were compared in cats, using several otoxicity assessment techniques. Daily subcutaneous doses of 90 and 45 mg of amikacin per kg and 18 and 9 mg of gentamicin per kg (approximately six and three times the daily human dose) were administered to cats for extended periods of time until cochlear or vestibular dysfunction developed. Renal tissue damage and serum and perilymph antibiotic concentrations were also monitored. Amikacin selectively produced an impairment of cochlear function after an approximate cumulative dose of 3,600 mg/kg obtained after 41 days at 90 mg/kg per day or 78 days at 45 mg/kg per day, as determined by electrophysiological assessment. Gentamicin caused an impairment of vestibular function after an approximate cumulative dose of 700 mg/kg obtained after 42 days at 18 mg/kg per day or 68 days at 9 mg/kg per day, as determined by ataxia and impaired righting reflex. Gentamicin also moderately reduced electrophysiological cochlear responses and appeared to cause histological renal tissue change more frequently than did amikacin.
使用几种耳毒性评估技术,在猫身上比较了两种氨基糖苷类抗生素阿米卡星和庆大霉素的耳毒性潜力。每天分别以每千克90毫克和45毫克的剂量给猫皮下注射阿米卡星,以及每天分别以每千克18毫克和9毫克的剂量给猫皮下注射庆大霉素(约为人类日剂量的六倍和三倍),持续较长时间,直至出现耳蜗或前庭功能障碍。同时监测肾脏组织损伤以及血清和外淋巴中的抗生素浓度。通过电生理评估确定,在每天90毫克/千克的剂量下持续41天或每天45毫克/千克的剂量下持续78天后,当阿米卡星的累积剂量达到约3600毫克/千克时,会选择性地导致耳蜗功能受损。通过共济失调和翻正反射受损确定,在每天18毫克/千克的剂量下持续42天或每天9毫克/千克的剂量下持续68天后,当庆大霉素的累积剂量达到约700毫克/千克时,会导致前庭功能受损。庆大霉素还会适度降低耳蜗的电生理反应,并且与阿米卡星相比,似乎更频繁地引起肾脏组织的组织学变化。