地塞米松圆窗和全身给药后在豚鼠外淋巴液及血浆中的代谢动力学特征  

Dexamethasone Pharmacokinetics in Perilymph and Plasma of Guinea Pig After Topical Administration and Intracardial Injection

作　　者：吴皓[1] 杨军[1] 侯东明[1] 张顺国[2] 陈洁[1] 张萍[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,上海200092 [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：《听力学及言语疾病杂志》2005年第4期260-263,共4页Journal of Audiology and Speech Pathology

基　　金：上海市科委资助课题(034119819)

摘　　要：目的探讨经圆窗和全身给药后外淋巴液、血液中地塞米松(dexamethasone,DEX)的代谢动力学特征。方法将浸满DEX(10mgml)的明胶海绵颗粒放置在豚鼠圆窗龛内或心内注射DEX(0.5mgkg)。采集两种途径给药后1～6h豚鼠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DEX浓度。结果圆窗或心内注射给药后,豚鼠外淋巴液、血浆中的DEX浓度随时间的延长呈逐渐下降的趋势;圆窗给药后血浆中未检测到DEX。圆窗给药后DEX在外淋巴液中的浓度明显高于全身给药后外淋巴液中DEX的浓度(P=0.0035).圆窗给药后血浆中的DEX浓度明显低于全身给药后血浆中DEX的浓度(P=0.0096);全身给药后外淋巴液中的DEX浓度明显低于血浆中的浓度(P=0.0097)。DEX在外淋巴液中的生物半衰期为2.67h。结论圆窗给药后DEX能够有效地经圆窗膜渗透进入外淋巴液,其浓度明显高于全身给药后外淋巴液中的浓度。Objective To determine pharmacokinetics profiles of dexamethasone (DEX) in perilymph and plasma of guinea pig after topical and systemic administration.Methods A granule gelfoam soaked with DEX (10 mg/ml) was placed in the niche of round window of guinea pig; 0.5 mg/kg of DEX 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 DEX in the samples.Results After topical administration or intracardial injection of DEX, concentrations of drug in perilymph and plasma decreased gradually over time. DEX was not detectable in sample of plasma after topical administration. The concentration of DEX in perilymph after topical administration was significantly higher than that after intracardial injection (P=0.0035). The concentration of DEX in plasma after topical administration was significantly lower than that after intracardial injection (P=0.0096). After intracardial injection, the concentration of DEX in perilymph was significantly lower than that in plasma(P=0.0097). The half-life time of DEX in perilymph was 2.67 hours.Conclusion DEX could penetrate effectively through round window membrane into the cochlear fluid and reach a much higher concentration following topical administration as compared with systemic application.

关 键 词：地塞米松 给药途径 药物代谢动力学 

分 类 号：R764.35[医药卫生—耳鼻咽喉科]