Dexamethasone Pharmacokinetics in Guinea Pig Inner Ear Perilymph

Abstract

Aim: To study the dexamethasone pharmacokinetics in the inner ear perilymph of guinea pigs using high-pressure liquid chromatography. Methods: Sixty-five guinea pigs were divided into three groups. In the first group, the drug application protocol used an intra-abdominal dose of 0.5% dexamethasone 4 mg·kg^–1. In the second group, an intratympanic application dose of 0.5% dexamethasone 150 µl was used. The third group was the control group. The concentrations of dexamethasone in inner ear perilymph were determined by high-pressure liquid chromatography. Results: The perilymph concentration-time curves of dexamethasone conformed to a one-compartment open model after an intra-abdominal application. The C_maxwas 0.927 ± 0.008 mg·l^–1, the T_max1.47 ± 0.04 h, the T_1/2K 2.92 ± 0.056 h, the AUC 5.533 ± 0.05 mg·h·l^–1, the T_1/2Ka 0.47 ± 0.024 h. After an intratympanic application, the perilymph concentration-time curves of dexamethasone also conformed to a one-compartment open model. The C_maxwas 0.201 ± 0.006 mg·l^–1, the T_max 0.117 ± 0.06 h, the AUC 0.868 ± 0.004 mg·h·l^–1, the T_1/2K 2.918 ± 0.089 h, the T_1/2Ka 0.161 ± 0.009 h. Compared to the intra-abdominal application, the intratympanic application resulted in similar levels of inner ear perilymph drug concentrations in 30 min. Conclusion: Dexamethasone can penetrate the blood-labyrinthine barrier after intra-abdominal application. Dexamethasone can enter into perilymph after intratympanic application. Under the condition of the study, the intratympanic application resulted in a similar level of inner ear perilymph drug concentrations compared to the intra-abdominal application in 30 min.