Talamo J H, D'Amico D J, Hanninen L A, Kenyon K R, Shanks E T
Am J Ophthalmol. 1985 Dec 15;100(6):840-7. doi: 10.1016/s0002-9394(14)73377-x.
To study the effect of lens and vitreous surgery on the dose threshold of aminoglycoside-induced retinal toxicity, we performed extracapsular lens extraction (Group 1) or lensectomy and vitrectomy (Group 2) on Dutch Belted rabbits. A single dose of amikacin or gentamicin ranging from 100 to 4,000 micrograms was administered intravitreally. Retinal toxicity was examined by light and transmission electron microscopy seven days after injection. Both groups showed retinal toxicity after 400 micrograms of gentamicin or 1,500 micrograms of amikacin, doses identical to those causing toxicity in intact, phakic rabbit eyes. Thus, neither surgical procedure increased the toxic threshold of injected aminoglycoside. Given the accelerated aminoglycoside clearance reported in aphakic eyes, these findings imply that the mechanism of aminoglycoside toxicity may be related to peak drug concentration rather than duration of tissue exposure.
为研究晶状体和玻璃体手术对氨基糖苷类药物所致视网膜毒性剂量阈值的影响,我们对荷兰带兔进行了囊外晶状体摘除术(第1组)或晶状体切除术联合玻璃体切除术(第2组)。玻璃体内注射单剂量范围为100至4000微克的阿米卡星或庆大霉素。注射七天后,通过光学显微镜和透射电子显微镜检查视网膜毒性。两组在注射400微克庆大霉素或1500微克阿米卡星后均出现视网膜毒性,这些剂量与在完整、有晶状体兔眼中引起毒性的剂量相同。因此,两种手术操作均未提高注射氨基糖苷类药物的毒性阈值。鉴于无晶状体眼中氨基糖苷类药物清除加速的报道,这些发现表明氨基糖苷类药物毒性机制可能与药物峰值浓度而非组织暴露持续时间有关。