Brummett R E
Rev Infect Dis. 1981 Nov-Dec;3 suppl:S216-23.
The guinea pig model has been useful for estimating quantitatively the ototoxic effects of many different drugs. Our model utilizes measures of the Preyer pinna reflex, the alternating current cochlear potential and sensory hair-cell morphology to access drug effects. The principle pathophysiologic lesion of aminoglycoside-induced permanent ototoxicity appears to be sensory hair-cell loss in the organ of Corti. Aminoglycoside antibiotics were found to interact with loop-inhibiting diuretics, and the augmented ototoxic effects were attributed to hair-cell destruction. The interaction is specific for loop-inhibiting diuretics but not for the aminoglycosides since nonaminoglycoside antibiotics, such as viomycin and polymixin B, interacted similarly. Noninteractive antibiotics include amphotericin B and vancomycin. The absence of ototoxic effects with vancomycin is of interest in view of its broadening clinical utility.
豚鼠模型对于定量评估多种不同药物的耳毒性作用很有用。我们的模型利用普赖尔耳廓反射、交流电耳蜗电位和感觉毛细胞形态学测量来评估药物作用。氨基糖苷类药物引起的永久性耳毒性的主要病理生理损伤似乎是柯蒂氏器中的感觉毛细胞丢失。发现氨基糖苷类抗生素与袢利尿剂相互作用，增强的耳毒性作用归因于毛细胞破坏。这种相互作用对袢利尿剂具有特异性，但对氨基糖苷类药物不具有特异性，因为非氨基糖苷类抗生素，如紫霉素和多粘菌素B，也有类似的相互作用。非相互作用的抗生素包括两性霉素B和万古霉素。鉴于万古霉素临床应用的不断扩大，其无耳毒性作用这一点很值得关注。
