Steroid intracochlear distribution differs by administration method: Systemic versus intratympanic injection

Abstract

NA. Laryngoscope, 128:189-194, 2018.

Comparison of the Effects of Intratympanic Steroid Injection at Different Intervals in Sudden Sensorineural Hearing Loss

“…In contrast, intratympanic steroid injection requires low concentrations of steroids, as the steroid is directly delivered through the round window [9]. Lee, et al [10] compared the steroid concentrations in the perilymph when dexamethasone was injected to mice through the round window or through the abdominal cavity and reported that injection through the round window results in higher steroid concentrations and maintains the concentration for a longer period of time. Therefore, despite intratympanic steroid injection being widely used in the clinical treatment of sudden sensorineural hearing loss, various opinions on the optimal dose, medication, and administration methods are still being proposed.…”

Advances and Challenges in Pharmaceutical Therapies to Prevent and Repair Cochlear Injuries From Noise

“…In general, local administration of MP or dexamethasone leads to greater perilymph concentration than systemic application (Bird et al, 2007; Yang et al, 2008; Grewal et al, 2013; Creber et al, 2018; Lee et al, 2018). For example, in humans, local IT administration of 40 mg of MP led to a 126-fold greater perilymph concentration after a single 1 mg/kg IV injection and 33-fold increase after 10 mg/kg IV infusion (Bird et al, 2007).…”

“…Additionally, higher and more prolonged intracochlear uptake was seen after administration of 3 IT injections of 20 μL of 10 mg/mL of fluorescein isothiocyanate-labeled dexamethasone in comparison to 3 i.p. injections of 60 μG/100 g (Lee et al, 2018). Tissue labeling after local administration mirrors glucocorticoid receptor distribution with the highest labeling in the SGNs, organ of Corti, and lateral walls (Lee et al, 2018) corresponding to the highest concentration of receptors in cochlear structures (Zuo et al, 1995).…”

“…injections of 60 μG/100 g (Lee et al, 2018). Tissue labeling after local administration mirrors glucocorticoid receptor distribution with the highest labeling in the SGNs, organ of Corti, and lateral walls (Lee et al, 2018) corresponding to the highest concentration of receptors in cochlear structures (Zuo et al, 1995). Dexamethasone perilymph elimination half-life has been calculated to be 111 min (Salt et al, 2012b) with peak glucocorticoid receptor activation, dexamethasone tissue labeling, and perilymph concentration 60 min after local application (Hargunani et al, 2006; Yang et al, 2008; Grewal et al, 2013).…”

“…After this, perilymph concentrations after IT injection show elimination from perilymph by around 6 h (Parnes et al, 1999; Bird et al, 2007; Yang et al, 2008). Dexamethasone labeling in cochlear tissue is present up to 7 days after administration (Lee et al, 2018), but significant decreases in uptake and labeling are seen by 12 h (Wang et al, 2011; Grewal et al, 2013). Greater dexamethasone uptake and immunofluorescent labeling has been reported in IHCs compared to OHCs in mice (Grewal et al, 2013), but this selective uptake has not been seen across species (Creber et al, 2018).…”