不同途径给药后血浆和外淋巴液中甲泼尼龙的代谢动力学特征  

Methylprednisolone pharmacokinetics in perilymph and plasma of guinea pig after topical administration and intracardial injection

作　　者：张萍[1] 吴皓[1] 杨军[1] 侯东明[1] 张顺国[2] 陈洁[1] 

机构地区：[1]上海第二医科大学附属新华医院耳鼻咽喉-头颈外科 [2]上海第二医科大学附属新华医院药剂科临床药理室

出　　处：《临床耳鼻咽喉科杂志》2005年第22期1040-1043,共4页Journal of Clinical Otorhinolaryngology

基　　金：上海市科委基金资助项目(No:034119819)

摘　　要：目的:探讨心内注射、鼓室内灌注、明胶海绵圆窗给药后血浆、外淋巴液中甲泼尼龙的代谢动力学特征.方法:心内注射甲泼尼龙(4 mg/kg);鼓室内灌注甲泼尼龙(40 g/L),浸满40 g/L溶液的明胶海绵颗粒放置在圆窗龛内分别给药,采集3种途径给药后1～6 h的血液和鼓阶外淋巴液,应用高效液相色谱仪分别检测其中的甲泼尼龙浓度.结果:心内注射给药后每个时间点血浆中的甲泼尼龙浓度均高于外淋巴液,两者相比差异有统计学意义,4～6 h时外淋巴液中已经检测不到甲泼尼龙.无论鼓室内灌注或明胶海绵圆窗给药后,在外淋巴液中检测到的甲泼尼龙浓度均明显高于心内注射给药者;鼓室内灌注或明胶海绵圆窗给药后,血浆中无可检测的甲泼尼龙.鼓室内灌注或明胶海绵圆窗给药后外淋巴液中甲泼尼龙的最高浓度出现于给药后1 h 20 min;在取材的每个时间点,鼓室内灌注给药后外淋巴液中的甲泼尼龙浓度均高于明胶海绵圆窗给药者,除4、6 h外,两者相比差异有统计学意义.鼓室内灌注给药后外淋巴液中甲泼尼龙的生物半衰期t1/2=1.51 h,明胶海绵圆窗给药后甲泼尼龙 t1/2=1.55 h.结论:局部给药后甲泼尼龙能够有效地经圆窗膜渗透进入外淋巴液,并能达到明显高于全身给药后外淋巴液中的浓度.鼓室内灌注给药后外淋巴液中的甲泼尼龙浓度较高.Objective t To determine pharmacokinetics profiles of methylprednisolone （MTH） in perilymph and plasma of guinea pig after topical and systemic administration. Method： A granule gelfoam soaked with MTH （40 mg/ml） was placed in the niche of round window of guinea pig; otocyst was infused with MTH （40 mg/ml） ; 4 mg/kg of MTH was injected intracardially. Samples of blood and perilymph of the scala tympani were obtained 1 6 h after administration of two routes, respectively. High-performance liquid chromatography was used to assay MTH in the samples. Result： After intracardial injection of MTH, concentrations of drug in plasma were obviously higher than those of in perilymph in every hour while drug in perilymph could not be obtainted in 4-6 h,and the results were significantly different. After niche was placed with granule gelfoam with drug or otocyst was infused with MTH, drug could not be obtained in plasma, concentrations of drug in perilymph were obviously higher than those of in plasma after intracardial injection,and the highest concentrations in perilymph were manifested in 1 h 20min. The concentrations of drug in perilimph after otocyst was infused with MTH were higher than those of after niche was placed with granule gelfoam soaked with MTH in every hour, and there were significant differences in between except those in 4 and 6 h. The half-life time of MTH in perilymph after otocyst was infused was 1.51 h,and the one after niche was placed with granule gelfoam soaked with MTH was 1.55 h. Conclusion： MTH could penetrate effectively through membrane of round window into the cochlear fluid and reach a much higher concentration following topical administration as compared with systemic application. The concentrations of drug in perilimph after otocyst was infused with MTH were higher.

关 键 词：甲泼尼龙 给药途径 药物代谢动力学 

分 类 号：R764.3[医药卫生—耳鼻咽喉科]