**2. History**

The delivery of medications to the inner ear through the transtympanic route dates back to 1935, when Barany (4) used intratympanic lidocaine for treatment of tinnitus. Since then, other molecules have been used and the indications have expanded. In 1948, streptomycin was used to treat patients with unilateral Meniere's disease specifically on the basis of its vestibulotoxic effects (5). It was Harold Schuknecht who proposed the use of streptomycin as an alternative to surgical unilateral labyrinthine ablation (6). Francis Bauer, in 1969 and 1971 reported on the treatment of "Glue Ear" by using intratympanic urea (7). Another

Intratympanic Corticosteroid for Neurosensorial Hearing Loss Treatment 385

The cochlea is surrounded by the petrous bone. It was shown that there is a direct exchange between the extracellular space of the petrous bone and perilymph through the lacuna canaliculi which are canals or holes in the bone in free communication with the scala

Treatment given by intratympanic will diffuse in liquid of the inner ear. There are 3 practical entry points: 1) through round window membrane RWM (at the base of the cochlea on the scala tympani side), 2) through or near the oval window (at the base of the cochlea on the scala vestibuli side), 3) through the bone of the cochlea via application in the middle ear.

The RWM has three layers (18): an outer epithelial layer on the middle ear side, a middle fibrous layer, and another epithelial layer facing the inner ear. The outer epithelial layer contains some microvilli and abundant mitochondria, suggesting that it may be able to absorb substances and carry out metabolic activities. The inner epithelial layer has areas of discontinuous basement membrane that may provide space for substances to traverse the

Plontke (19), and colleagues have extensively modeled the distribution of drugs applied at the RWM. They suggest that in addition to diffusion along the length of the cochlea, diffusion through the tissue of the cochlea from one scala to another must be considered as

Some factors facilitate the passage of molecules through the round window membrane: low molecular weight, water-soluble nature, the ionic charge, histamine, prostaglandins, leukotrienes, endotoxin of E. coli, Staphylococcus exotoxins (20). The contact time with the round window membrane has the most important effect. Wang (21) demonstrates that the inner ear pharmacokinetic profile of steroids administered intratympanically is dependent upon the nature of the vehicle as well as the physicochemical properties of the steroid drug itself. In fact the degree of aqueous solubility of the drug has a major impact on its residence

Glucocorticoid receptors have been identified in the inner ear and are more abundant in the cochlea (22). The presence of glucocorticoid receptors in the inner ear provides a cellular means by which circulating glucocorticoids can directly affect the inner ear physiology. Corticosteroids have been used extensively for inner ear disease because of their antiinflammatory effects but also affect the vascularity of the inner ear. Corticosteroids have many effects : they prevent a decrease in cochlear blood flow, reduce degeneration of the

Two corticosteroids are used by the majority of the researchers: dexamethasone and methylprednisolone. The concentration is varied between 4 mg/ ml and 25 mg/ml for

Parnes in pharmacokinetic animal study compared intracochlear levels of three glucocortiocoids: dexamethasone (Dexa), methylprednisolone (MP), and hydrocortisone

dexamethasone and between 32 mg/ ml and 62,5 mg/ml for methylprednisolone.

tympani (17).

membrane.

well.

**5. Pharmacokinetics and pharmacodynamics** 

This infusion is mainly through the round window.

time and exposure in the inner ear (21).

**6. Choice of drug** 

stria vascularis and have an antioxidant effect (23).

interesting application of intratympanic medication was reported by Bryan in 1973, when he described the use of intratympanic steroids in a patient with facial paralysis (8). Itoh (9), in 1991, used steroids for Meniere's disease. Silverstein (10) in 1996, used steroids for Sensorineural Hearing Loss.
