Cochlear hair cell loss in single-dose versus continuous round window administration of gentamicin

Conclusions. Gentamicin-induced cochlear hair cell loss depends on local middle ear administration kinetics and the total drug dose. Single-dose gentamicin instillation in the middle ear is associated with a high variation in hair cell loss. Objective. To compare the effects of single-dose and continuous round window administration of gentamicin on cochlear hair cell loss in a guinea pig model. Material and methods. Two methods for drug administration to the inner ear were used. In groups of five animals, a total dose of 0.8 or 3.2 mg of gentamicin was either instilled as a single dose directly into the round window niche or administered continuously over a 1-week period using a pump - catheter system. Continuous administration was achieved by means of a posterior tympanotomy and subcutaneous placement of an osmotic pump fitted with a catheter. The tip of the catheter was fixed in the round window niche. One group of five animals served as controls and received a saline infusion. The animals were sacrificed after 1 week and hair cell loss was determined microscopically after dissection and phalloidin labelling of the basilar membrane and organ of Corti. Results. Quantitation of cochlear hair cell loss revealed a dose-dependent effect of gentamicin. With both treatment modalities the higher dose induced a higher percentage of hair cell loss. There was inner and outer hair cell loss in all four groups that received gentamicin. With the single-dose instillation, hair cell loss was distributed irregularly from the round window membrane towards the cochlear apex, whereas continuous administration induced hair cell loss close to the round window membrane. Single-dose instillation induced greater hair cell loss than continuous administration at the same dose. The inter-individual variation in hair cell loss was highest following single-dose instillation.