The Pharmacokinetic Profiles Of Steroid Hormones In Perilymph And Plasma Of Guinea Pig Following Local Administration With Different Concentrations Of Steroid Hormones

Objective To determine pharmacokinetics profiles of methylprednisolone(MTH) and dexamethasone(DEX) in perilymph and plasma of guinea pig after intratympanic injection of MTH and DEX with different concentrations.Method By auripuncture,three concentrations of MTH were used in guinea pigs: 32mg/ml,40mg/ml and 62.Smg/ml,and also three concentrations of DEX:5mg/ml, 10mg/ml and 15mg/ml.Samples of blood and perilymph of the scala tympani were collected at 1-12h after administration.Highperformance liquid chromatography(HPLC) was used to assay concentrations of MTH and DEX in the blood and perilymph. Auditory brainstem response(ABR) was detected at the time before the injection and the sample collection.Results 1.Each time when samples were collected,except 5h,6h and 12h,the differences in concentrations of MTH in the perilymph after MTH administration in the three concentrations have significant statistical sense(P＜0.05).2.Each time when samples were collected,the differences in concentrations of DEX in the perilymph after the 5mg/ml and 10mg/ml,15mg/ml of DEX intratympanic administration have significant statistical sense(P＜0.01).At the sampling times of 1h,1.30h and 2h,the differences in concentrations of DEX in the perilymph after the 10mg/ml and 15mg/ml of DEX intratympanic administration have statistical sense(P＜0.05). 3.When using the three concentrations of MTH,there was not significant difference between the time before the injection and the sample collection in ABR thresholds of waveⅢ(p＞0.05).4.When using the 5mg/ml and 10mg/ml of DEX,there was not significant difference between the time before the injection and the sample collection in ABR thresholds of waveⅢ(p＞0.05).While using the 15mg/ml of DEX,there was significant difference between the time before the injection and the sample collection in ABR thresholds of waveⅢ(p=0.038,p＜0.05).Conclusion As can be seen from the experimental results,after intratympanic injection with the 62.5mg/ml of MTH,there got the highest concentration in perilymph,the biggest area under the curve(AUC),the most amount of absorption in inner ear tissues and also the highest biological availability,while no effect on cochlear function was found.The 10mg/ml of DEX in the three concentrations of DEX is the best one to treat inner ear diseases by intratympanic administration.The 15mg/ml of DEX have effects on cochlear function to some extent.