When drugs are applied intratympanically (into the middle ear) a small proportion diffuses into the inner ear. How much enters and how it distributes is controlled by 3 main factors, as shown in the illustration below.


1) Middle Ear elimination to the vasculature

2) Entry characteristics of the Round Window Membrane

3) Elimination from scala tympani perilymph to the vasculature.

We have developed an Excel spreadsheet that calculates these 3 processes, allowing different drug and application scenarios to be compared. Calculations can be performed to represent ANY DRUG, using PK parameters estaimated from molecular properties of the drug.

The Excel spreadsheet (v2.2, Feb 25th, 2020) and instructions can be downloaded here

The spreadsheet uses macros to transfer parameters into the calculation page. If you don’t want to enable macros, the spreadsheet will still all work fine except for the parameter transfer buttons which will be disabled.

 The spreadsheet allows two drugs with different properties to be compared, in this case triamcinolone compared to triamcinolone-acetonide. The two forms have completely different properties which , for longer times, allows triamcinolone to distribute along the cochlea (blue curves, 24 hour panel) while triamcinolone-acetonide does not (red curves, 24 hour panel). It is notable that perilymph concentration measured after 1 hour application would be almost identical for the two drugs, even though their kinetics are completely different. This is an example of the "Serial Barriers Problem" as discussed here

 The example below compares the kinetics of dexamethasone suspension and dexamethasone-phosphate, the commonly applied form of the drug. Dexamethsone-phosphate is lost rapidly from the middle ear so it only has time to distribute briefly in the basal part of the cochlea. Dexamethasone spreads further, but still only part of the distance along the cochlea, as it is lost rapidly to the vasculature.

It is apparent that dexamethasone-phosphate only briefly treats the basal partion of the cochlea, with none reaching apical regions. Similarly, dexamethasone suspension does not distribute to apical regions.

The spreadsheet provides a teaching tool, to describe the main parameters that influence drug distribution in the ear.

Pharmacokinetic predictions can be performed for ANY DRUG, by following instructions on the "Find Parameters" page

Enter the properties of the drug (obtained from the SwissADME website, as explained on the sheet) and the spreadsheet will calculate kinetic properties for the ear, based on measurements with other molecules that have been studied.