Analysis of gentamicin kinetics in fluids of the inner ear with round window administration

 

 
 
 

Stefan K.R. Plontke*, Arthur W. Wood and Alec N. Salt

 

 
 

Abstract

Hypothesis: That a theoretical basis for quantifying drug distribution in the inner ear with local applications can be established.
Background: As methods of local drug delivery to the inner ear gain wider clinical acceptance, it becomes important to establish how drugs are distributed in the ear as a function of time and for different delivery methods.
Methods: The time course of gentamicin concentration in the inner ear fluids was simulated with a program considering general pharmacokinetic principles and incorporating inner ear dimensions and drug dispersal processes, including diffusion, clearance and inter-compartmental exchange.
Results: Cochlear fluid space dimensions of the chinchilla were derived from 3-dimensional magnetic resonance images and were incorporated into the simulator. The published time course of gentamicin in vestibular perilymph of chinchillas was closely approximated by the adjustment of parameters defining round window membrane permeability, clearance and inter-scala exchange. To simulate the time course it was necessary for drug entry into the vestibule to be dominated by inter-scala exchange rather than longitudinal spread through the helicotrema. The effects of different round window delivery methods were also calculated. Perilymph drug levels and spatial distribution in the ear were shown to be markedly influenced by the time the applied drug remained in the middle ear.
Conclusion: Development of local inner ear drug application strategies requires consideration of inner ear pharmacokinetic characteristics, delivery methods and therapeutic range of the drug.
 
 

This study was supported by the National Institutes of Health through the National Institute on Deafness and other Communication Disorders, Grant number DC01368

---

Back to Publications page