不同途径给药后豚鼠外淋巴液中甲泼尼龙琥珀酸钠的代谢动力学特征-耳鼻咽喉科学专业论文.docxVIP

安徽医科大学硕士学位论文 安徽医科大学硕士学位论文 PAGE PAGE 1 英文缩略词表（Abbreviation） 英文缩写 英文全称 中文全称 MTH MRS Methylprednisolone Methylprednisolone Reference Substance 甲泼尼龙琥珀酸钠 甲泼尼龙琥珀酸钠对照品 MCRS Hydrogenated Cortisone Reference Substance 氢化可的松对照品 SP Sodium Pentobarbital 戊巴比妥钠 HLM Hydrochloric Lee May 盐酸利多可因 AS Ammonium Sulfate 硫酸铵 M Methanol 甲醇 A Acetonitrile 乙腈 摘 要 目的:探讨鼓室内灌注、明胶海绵经圆窗给药后豚鼠外淋巴液中甲泼尼龙 琥珀酸钠（methylprednisolone，MTH)的代谢动力学特征，为临床选 择经鼓室给药方式提供实验依据。 方法:采用鼓室内灌注 MTH (62.5mg/ml) 及将浸满 MTH（62.5mg/ml ）的 明胶海绵放置于圆窗上两种方式给药,采集 2 种途径给药后 1～12 h 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:鼓室内灌注或明胶海绵经圆窗给药后外淋巴液中 MTH 的最高浓度 均出现在给药后 1.5h ;在取材的每个时间点,鼓室内灌注给药后外淋 巴液中的 MTH 浓度均高于明胶海绵经圆窗给药者,除 5、6 及 12h 外,两者相比差异均有统计学意义。鼓室内灌注给药后外淋巴液中 MTH 的生物半衰期 t1/ 2 = 1. 84h ,明胶海绵圆窗给药后甲泼尼龙 t1/ 2 = 1. 87 h。鼓室内灌注、明胶海绵经圆窗给药后 12 h 取材时间点 的豚鼠较给药前与取外淋巴前 ABR 波形Ⅲ波阈值比较差异均无统 计学意义(P 值均0．05)。 结论:局部给药后 MTH 能够有效地经圆窗膜渗透进入外淋巴液。鼓室内 灌注给药后外淋巴液中的甲泼尼龙浓度较高。该浓度的 MTH 对内耳 功能未见明显影响。 [关键词] 甲泼尼龙琥珀酸钠;给药途径;药物代谢动力学 Methylprednisolone pharmacokinetics in perilymph of guinea pig after different topical administrations GAO Hong 1，WANG Yin-feng1,WANG ya-lin2 (1Department of Otorhinolaryngology and Head-neck Surgery ,Anhui Provincial Hospita ,Anhui Medical University； 2Department of Otorhinolaryngology and Head-neck Surgery，Anhui Provincial Hospital；230001．China，) Abstract Objective :To determine pharmacokinetics profiles of methylprednisolone (MTH) in perilymph of guinea pig with different intratympanic administrations，and to provide experimental evidence for clinical choice about administration Method : Two different topical administrations infusing otocyst with MTH solution(62.5mg/ml) and placing a granule gelfoam soaked with MTH(62.5mg/ml)in the round window niche of guinea pig were conducted． Samples of perilymph of the scala tympani were obtained 1～12h after administration of two routes , respectively. Highperformance liquid chromatography was used to assay MTH in the samples. Result : After niche was placed with granule gelfoam with drug or otocyst was inffused with