Dexamethasone concentration in perilymph following post-aural or intratympanic Injection

SHI Jiao; HAN Lin; LI Jingjing; JING Yuanyuan; ZHENG Hongwei; YU Lisheng

doi:10.3969/j.issn.1672-2922.2016.04.022

Abstract：Objective To compare dexamethasone concentration in the perilymph (PL) after post-aural or intratym-panic injection in guinea pigs. Methods Dexamethasone sodium phosphate (10 mg/ml) was injected post-aurally (1 ml) or intratympanically (0.1 ml) in guinea pigs. Samples of perilymph were obtained at 0.25, 0.5, 1, 2.5, 5, 6 and 8 hours after post-aural injection and at 0.5, 1, 2, 3, 4, 6 and 8 hours after intratympanic injection respectively. High-performance liquid chromatography(HPLC)was used to assay dexamethasone concentration in the samples. Results ①dexamethasone was de-tected in the inner ear following both modes of injection;②Following intratympanic injection, active pharmaceutical ingre-dients were detected from 0.5 to 8 hours in the perilymph, peaking at 3 hours with a peak concentration (Cmax) of 906.55mg/l and a biological half-life of 1.27 hours.③After post-aural injection, dexamethasone was detected from 0.25 to 8 hours with a peak time (Tmax) at 0.25 hour, a Cmax at 18.83 mg/l and a biological half-life of 3.36 hours.④The peri-lymph dexamethasone concentration was lower but half-life longer after post-aural injection than after intratympanic admin-istration. Conclusion Drugs may enter the perilymph space by various ways after post-aural injection, although drug concen-tration may be relatively lower compared to intratympanic administration. As the intratympanic route bypasses the blood-brain and blood-labyrinth barriers, drugs through this route may gain access into the perilymph faster and reach high-er concentrations than when given via post-aural injection. Clinical observation, however, seems to suggest that onset of cor-ticoids effects may start at a relatively low concentration in the perilymph.