Fig. 5.

Concentration gradients for two different application strategies. RWM = Round window membrane. A A basal-apical gradient persists even after continuous application of a substance to the base of the scala tympani for 10 days. High concentrations are found at the high frequency region of the cochlea compared to low concentrations at the low frequency region of the cochlea. Radial concentration gradients across the scalae and spiral ligament are also apparent. They are more pronounced in the basal compared to the apical part. B After a 30-min application time a much larger concentration gradient between the basal and apical regions of the cochlea is found. C Same application as in B but scaled up by a factor of 2.5. After stop of the brief application the gradients across the scalae in the base and between basal and apical regions are both diminished, even though the drug levels throughout the cochlea at this time are much lower compared to a continuous application strategy. Note that longitudinal concentration gradients and distribution in cross-sectional area are determined by pharmacokinetic parameters specific for the applied substance (i.e. diffusion coefficient, clearance and permeability of the boundaries between the various compartments).