**1.5 The experience in using glucocorticoids in PDT patients**

This study was the first study which was carried out in the Institute of Physiology and Pathology of Hearing World Hearing Center and will be continued with different groups of patients and different implants and algorithms of glucocorticoid administration. The aim of the study was to evaluate different regimes of administration of glucocorticoids: dexamethasone and dexamethasone/prednisone to *partial deafness* treatment (PDT) patients who underwent cochlear implantation on the hearing preservation. Implant used in the study was the MED-EL implant with an electrode length of 28 mm (Flex 28). The impact of administrated glucocorticoids on hearing was measured in six different periods:


Forty-six patients were enrolled to the trial and then divided randomly into three subgroups. Patients from the first subgroup underwent intravenous steroid therapy (**Figure 1**). According to the scheme, 30 min before implantation, dexamethasone at the dose of 0.1 mg/kg body mass was administrated intravenously to patients from the first subgroup. For the next 3 consecutive days in every 12 h, dexamethasone was administrated intravenously at the same dose to each patient.

Patients from the second subgroup underwent prolonged (combined) steroid therapy: oral and intravenous. Three days prior to the surgery, prednisone was administrated orally at a dose of 1 mg/kg body mass/day. Then, 30 min before the cochlear implantation surgery, dexamethasone was administrated intravenously at a dose of 0.1 mg/kg body mass. For the next 3 consecutive days in every 12 h, dexamethasone was administrated intravenously (the same as in the first subgroup). For the next 3 days, prednisone was administrated orally at the dose of 1 mg/kg body mass/day. After this period, the dose of prednisone was reduced (10 mg per every

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preservation.

*Role of Glucocorticoids in Hearing Preservation in Partial Deafness Treatment*

day) till complete reduction of dose, due to reducing the risk of adverse effects. The algorithm of administration of glucocorticoids to patients form the second sub-

The third subgroup was a control group and underwent standard cochlear

Only 2.6% of the chemically unchanged dose is eliminated via kidneys.

medical products: dexamethasone and prednisone.

**and exclusion criteria**

According to the protocol of this study, two different algorithms of administration with two different glucocorticoids were proposed in the study. Although both substances belong to the same pharmacological group, both of them have different pharmacokinetics and pharmacodynamic properties. Dexamethasone is a synthetic glucocorticoid (*molecular weight 392.46 g/mol*) with anti-inflammatory, anti-allergic, and immunomodulating activity. In common practice dexamethasone is administrated *intravenously* or off-label, e.g., *transtympanic injections*. After *intravenous* administration the mean time to peak concentration (Cmax) is between 10 and 30 min, and the half-life (t1/2) is from 2.2 to 3.8 h. Transport proteins are responsible for transport and distribution of dexamethasone in blood. Dexamethasone is mainly metabolized by the liver and eliminated with the bile.

Prednisone is a synthetic glucocorticoid (derivative of cortisone) and classified according to the *Anatomical Therapeutic Chemical (ATC) Classification System* as H02 AB 07. Prednisone is *prodrug* which converts into *active metabolite—prednisolone* (higher anti-inflammatory activity). According to characteristic of medical product and literature data, bioavailability of prednisone administrated orally is between 70 and 90%. The mean time to peak concentration (Cmax) is between 1 and 2 h. Half-life (t1/2) is between 3.4 and 3.8 h in plasma and 18–36 h in tissue. Binding prednisone with plasma proteins is between 70 and 73% (binding prednisolone (active metabolite) to the plasma proteins is higher (90–95%)). Similar to dexamethasone, prednisone is metabolized mainly by the liver and eliminated with the bile. Pharmacodynamic and pharmacokinetic data were based on characteristics of

**1.7 Methodology of the study: primary and secondary outcomes and inclusion** 

The primary outcome variables were mean values of hearing thresholds averaged across all 11 frequencies (125–8000 Hz). The secondary outcome variable was hearing preservation (HP). Hearing preservation (HP) was calculated by comparing hearing thresholds in the 1-year postoperative period with the preoperative hearing thresholds, according to the hearing preservation (HP) formula (below) and converted to three levels: minimal, partial, and complete hearing

*DOI: http://dx.doi.org/10.5772/intechopen.88863*

*Scheme of steroid administration in the second subgroup of patients.*

group is presented below (**Figure 2**).

**1.6 Administrated glucocorticoids**

implantation procedure [18].

**Figure 2.**

#### **Figure 1.**

*Scheme of steroid administration in the first subgroup of patients.*

*Role of Glucocorticoids in Hearing Preservation in Partial Deafness Treatment DOI: http://dx.doi.org/10.5772/intechopen.88863*

**Figure 2.** *Scheme of steroid administration in the second subgroup of patients.*

day) till complete reduction of dose, due to reducing the risk of adverse effects. The algorithm of administration of glucocorticoids to patients form the second subgroup is presented below (**Figure 2**).

The third subgroup was a control group and underwent standard cochlear implantation procedure [18].
