Intratympanic Versus Intravenous Delivery of Methylprednisolone to Cochlear Perilymph

TLDR

The study compares perilymph and plasma methylprednisolone levels after intratympanic versus intravenous delivery. Perilymph and plasma were sampled 0.5–3 h after administering 40 mg IT, 1 mg/kg IV bolus, or 10 mg/kg IV infusion, and methylprednisolone levels were quantified by HPLC. IT delivery produced perilymph concentrations 126‑fold (vs 1 mg/kg IV) and 33‑fold (vs 10 mg/kg IV) higher, while plasma levels were 16‑fold and 136‑fold lower, demonstrating that intratympanic administration achieves superior cochlear exposure with reduced systemic exposure.

Abstract

Objective: To compare methylprednisolone concentrations in the perilymph of the human ear and in plasma after intratympanic (IT) or intravenous (IV) administration. Methods: Methylprednisolone concentrations in the perilymph of patients during cochlear implantation were compared after 3 dosing strategies of methylprednisolone solution for injection (40 mg/ml): 1) IT administration of up to 40 mg was injected into the middle ear through the external auditory canal via a 27-gauge needle passed through a small anterosuperior myringotomy; 2) IV administration of 1 mg/kg was given as a single injection over 30 seconds; 3) IV administration of 10 mg/kg was infused over 30 minutes. Perilymph (single sample, ~20 μL) was sampled using a needle passed through the round window membrane, from 0.5 to 3 hours after dosing. In most patients, simultaneous blood sampling was performed. Methylprednisolone concentrations were measured by high-performance liquid chromatography with a limit of quantification of 0.001 mg/L. Results: In 39 patients studied, 33 perilymph samples were suitable for measurement, along with 26 plasma samples. Median perilymph concentrations were 6.7 mg/L (n = 18; range, 0.2-89.4 mg/L) after IT administration, 0.053 mg/L (n = 8; range, 0-0.47 mg/L) after IV injection of 1 mg/kg, and 0.2 mg/L (n = 7; range, 0.067-3.1 mg/L) after IV infusion of 10 mg/kg. The median perilymph concentrations were 126-fold higher after the IT administration than after 1 mg/kg IV (p = 0.0003) and 33-fold higher than after 10 mg/kg IV infusion (p = 0.0045). Plasma concentrations after IT administration were 16-fold lower than after IV administration of 1 mg/kg (p = 0.0006), and 136-fold lower than after IV infusion of 10 mg/kg (p = 0.0006). Conclusion: IT administration of methylprednisolone in humans results in much higher perilymph concentrations and much lower systemic concentrations than IV administration.