Morphologic changes in the inner ear of Chinchilla laniger after middle ear administration of gentamicin in a sustained-release vehicle.

The use of transtympanic gentamicin has become a popular method of treating Meniere's disease; nevertheless, many questions still remain regarding this therapy. Until investigators can control the exact amount of medicine that is administered to the ear and have an understanding of the kinetics of gentamicin, therapy will continue to rely on empirical data. Previously we described the use of a fibrin-based sustained-release vehicle impregnated with gentamicin in the middle ears of chinchillas. With this model a kinetics curve of gentamicin was defined. The inner ears of these animals were submitted for immunohistochemical and histologic analysis. We discuss the ultrastructural changes seen and correlate this to our kinetics data. We also examine measurement of hair cell damage with heat shock protein levels. By better understanding the actions of gentamicin in this animal model, we hope to facilitate safer use of intratympanic medicines in our patient population.

Kinetics of gentamicin uptake in the inner ear of Chinchilla langier after middle-ear administration in a sustained-release vehicle.

The search for a safe, effective treatment for the vertigo associated with Meniere's disease has long been an important topic in otolaryngology. In recent years many groups have begun using intratympanic gentamicin to treat this vertigo. Although reported cure rates are as high as 90%, many questions remain regarding this type of treatment. Current limitations are the necessity for repeated treatments and a lack of clear dosing guidelines. In addition, the gentamicin must be delivered in a manner that allows maximal vestibulotoxic effect without injury to hearing. Until investigators can control the exact amount of medicine that is placed in the ear and have an understanding of the kinetics of gentamicin absorption, adequate dosing guidelines will be difficult to establish, and therapy will continue to rely on empiric data. We describe the use of a fibrin-based sustained-release vehicle, impregnated with gentamicin, injected into the middle ear of chinchillas. This allows for a prolonged effect without repeated dosing. Using this model, we studied the absorption kinetics of gentamicin at time points ranging from 8 hours to 1 week after injection. We used our findings to create a kinetics curve of gentamicin absorption. We discuss the shape and characteristics of this kinetics curve and examine the effects of the fibrin-based sustained-release vehicle and gentamicin on the middle ear. We noted no absorption in the contralateral (untreated ear) or blood. Through better understanding of the actions of gentamicin in this animal model, we hope to facilitate safer use of intratympanic medicines in our patient population and initiate programs for the use of this sustained-release vehicle in human beings.